572:(NHEJ), resulting in gene disruptions through the introduction of small insertions or deletions. Each repeat is conserved, with the exception of the so-called repeat variable di-residues (RVDs) at amino acid positions 12 and 13. The RVDs determine the DNA sequence to which the TALE will bind. This simple one-to-one correspondence between the TALE repeats and the corresponding DNA sequence makes the process of assembling repeat arrays to recognize novel DNA sequences straightforward. These TALEs can be fused to the catalytic domain from a DNA nuclease, FokI, to generate a transcription activator-like effector nuclease (TALEN). The resultant TALEN constructs combine specificity and activity, effectively generating engineered sequence-specific nucleases that bind and cleave DNA sequences only at pre-selected sites. The TALEN target recognition system is based on an easy-to-predict code. TAL nucleases are specific to their target due in part to the length of their 30+ base pairs binding site. TALEN can be performed within a 6 base pairs range of any single nucleotide in the entire genome.
518:. Each finger of the Zinc finger domain is completely independent and the binding capacity of one finger is impacted by its neighbor. TALEs on the other hand are found in repeats with a one-to-one recognition ratio between the amino acids and the recognized nucleotide pairs. Because both zinc fingers and TALEs happen in repeated patterns, different combinations can be tried to create a wide variety of sequence specificities. Zinc fingers have been more established in these terms and approaches such as modular assembly (where Zinc fingers correlated with a triplet sequence are attached in a row to cover the required sequence), OPEN (low-stringency selection of peptide domains vs. triplet nucleotides followed by high-stringency selections of peptide combination vs. the final target in bacterial systems), and bacterial one-hybrid screening of zinc finger libraries among other methods have been used to make site specific nucleases.
673:) followed by outgrowth, during which bacteriophage homologous recombination proteins mediate annealing of ssDNAs to their genomic targets. Experiments targeting selective phenotypic markers are screened and identified by plating the cells on differential medias. Each cycle ultimately takes 2.5 hours to process, with additional time required to grow isogenic cultures and characterize mutations. By iteratively introducing libraries of mutagenic ssDNAs targeting multiple sites, MAGE can generate combinatorial genetic diversity in a cell population. There can be up to 50 genome edits, from single nucleotide base pairs to whole genome or gene networks simultaneously with results in a matter of days.
353:
657:
1365:" – to perform their own experiments, posing a potential risk from the release of genetically modified bugs. The review also found that the risks and benefits of modifying a person's genome – and having those changes pass on to future generations – are so complex that they demand urgent ethical scrutiny. Such modifications might have unintended consequences which could harm not only the child, but also their future children, as the altered gene would be in their sperm or eggs. In 2001 Australian researchers Ronald Jackson and Ian Ramshaw were criticized for publishing a paper in the
559:(TALENs) are specific DNA-binding proteins that feature an array of 33 or 34-amino acid repeats. TALENs are artificial restriction enzymes designed by fusing the DNA cutting domain of a nuclease to TALE domains, which can be tailored to specifically recognize a unique DNA sequence. These fusion proteins serve as readily targetable "DNA scissors" for gene editing applications that enable to perform targeted genome modifications such as sequence insertion, deletion, repair and replacement in living cells. The DNA binding domains, which can be designed to bind any desired DNA sequence, comes from
20:
1354:, stating that genome editing conducted by countries with regulatory or ethical standards "different from Western countries" probably increases the risk of the creation of harmful biological agents or products. According to the statement the broad distribution, low cost, and accelerated pace of development of this technology, its deliberate or unintentional misuse might lead to far-reaching economic and national security implications. For instance technologies such as CRISPR could be used to make "killer mosquitoes" that cause plagues that wipe out staple crops.
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observe the phenotype, and start the process over with a different single-gene manipulation. Therefore, researchers at the Wyss
Institute at Harvard University designed the MAGE, a powerful technology that improves the process of in vivo genome editing. It allows for quick and efficient manipulations of a genome, all happening in a machine small enough to put on top of a small kitchen table. Those mutations combine with the variation that naturally occurs during cell mitosis creating billions of cellular mutations.
809:
640:
cheapest method, only costing less than two hundred dollars and a few days of time. CRISPR also requires the least amount of expertise in molecular biology as the design lays in the guide RNA instead of the proteins. One major advantage that CRISPR has over the ZFN and TALEN methods is that it can be directed to target different DNA sequences using its ~80nt CRISPR sgRNAs, while both ZFN and TALEN methods required construction and testing of the proteins created for targeting each DNA sequence.
820:, ZFNs, and TALEN provides a new strategy for genetic manipulation in plants and are likely to assist in the engineering of desired plant traits by modifying endogenous genes. For instance, site-specific gene addition in major crop species can be used for 'trait stacking' whereby several desired traits are physically linked to ensure their co-segregation during the breeding processes. Progress in such cases have been recently reported in
393:
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combinations that offer the best specificity and the best cell tolerance. Although the direct genome-wide characterization of zinc finger nuclease activity has not been reported, an assay that measures the total number of double-strand DNA breaks in cells found that only one to two such breaks occur above background in cells treated with zinc finger nucleases with a 24 bp composite recognition site and obligate heterodimer
473:
to find an endonuclease whose DNA recognition site and cleaving site were separate from each other, a situation that is not the most common among restriction enzymes. Once this enzyme was found, its cleaving portion could be separated which would be very non-specific as it would have no recognition ability. This portion could then be linked to sequence recognizing peptides that could lead to very high specificity.
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213:-compliant regulation to rules closer to those of the US and some other countries. An April 2021 European Commission report found "strong indications" that the current regulatory regime was not appropriate for gene editing. Later in 2021, researchers announced a CRISPR alternative, labeled obligate mobile element–guided activity (OMEGA) proteins including IscB, IsrB and TnpB as endonucleases found in
514:
recognition peptide. ZFNs rely on Cys2-His2 zinc fingers and TALEN constructs on TALEs. Both of these DNA recognizing peptide domains have the characteristic that they are naturally found in combinations in their proteins. Cys2-His2 Zinc fingers typically happen in repeats that are 3 bp apart and are found in diverse combinations in a variety of nucleic acid interacting proteins such as
800:
expression analysis has resolved a transcriptional road-map of human development from which key candidate genes are being identified for functional studies. Using global transcriptomics data to guide experimentation, the CRISPR based genome editing tool has made it feasible to disrupt or remove key genes in order to elucidate function in a human setting.
486:. The zinc ion, found in 8% of all human proteins, plays an important role in the organization of their three-dimensional structure. In transcription factors, it is most often located at the protein-DNA interaction sites, where it stabilizes the motif. The C-terminal part of each finger is responsible for the specific recognition of the DNA sequence.
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836:(PAT) into the targeted endogenous locus IPK1 in this case. Such genome modification observed in the regenerated plants has been shown to be inheritable and was transmitted to the next generation. A potentially successful example of the application of genome editing techniques in crop improvement can be found in banana, where scientists used
832:, using ZFN-assisted gene targeting, two herbicide-resistant genes (tobacco acetolactate synthase SuRA and SuRB) were introduced to SuR loci with as high as 2% transformed cells with mutations. In Zea mays, disruption of the target locus was achieved by ZFN-induced DSBs and the resulting NHEJ. ZFN was also used to drive herbicide-tolerance
335:, it is possible to knock out or switch on genes only in certain cells. These techniques were also used to remove marker genes from transgenic animals. Further modifications of these systems allowed researchers to induce recombination only under certain conditions, allowing genes to be knocked out or expressed at desired times or
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system, the programmed Cas9 protein and the sgRNA can be directly introduced into fertilized zygotes to achieve the desired gene modifications when creating transgenic models in rodents. This allows bypassing of the usual cell targeting stage in generating transgenic lines, and as a result, it reduces generation time by 90%.
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gene. It has been demonstrated that this strategy can be used to promote a process of angiogenesis in animals. It is also possible to fuse a protein constructed in this way with the catalytic domain of an endonuclease in order to induce a targeted DNA break, and therefore to use these proteins as genome engineering tools.
705:
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ZFN-mediated mutants and the improvements in TALEN-based approaches testify to the significance of the methods, and the list is expanding rapidly. Genome editing with engineered nucleases will likely contribute to many fields of life sciences from studying gene functions in plants and animals to gene
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As opposed to meganucleases, the concept behind ZFNs and TALEN technology is based on a non-specific DNA cutting catalytic domain, which can then be linked to specific DNA sequence recognizing peptides such as zinc fingers and transcription activator-like effectors (TALEs). The first step to this was
448:
methods have been used to create meganuclease variants that recognize unique sequences. Others have been able to fuse various meganucleases and create hybrid enzymes that recognize a new sequence. Yet others have attempted to alter the DNA interacting aminoacids of the meganuclease to design sequence
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Although GEEN has higher efficiency than many other methods in reverse genetics, it is still not highly efficient; in many cases less than half of the treated populations obtain the desired changes. For example, when one is planning to use the cell's NHEJ to create a mutation, the cell's HDR systems
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Because of the ease of use and cost-efficiency of CRISPR, extensive research is currently being done on it. There are now more publications on CRISPR than ZFN and TALEN despite how recent the discovery of CRISPR is. Both CRISPR and TALEN are favored to be the choices to be implemented in large-scale
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Furthermore, gene editing can be applied to certain types of fish in aquaculture such as
Atlantic salmon. Gene editing in fish is currently experimental, but the possibilities include growth, disease resistance, sterility, controlled reproduction, and colour. Selecting for these traits can allow for
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MAGE experiments can be divided into three classes, characterized by varying degrees of scale and complexity: (i) many target sites, single genetic mutations; (ii) single target site, many genetic mutations; and (iii) many target sites, many genetic mutations. An example of class three was reflected
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Meganucleases method of gene editing is the least efficient of the methods mentioned above. Due to the nature of its DNA-binding element and the cleaving element, it is limited to recognizing one potential target every 1,000 nucleotides. ZFN was developed to overcome the limitations of meganuclease.
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Several approaches are used to design specific zinc finger nucleases for the chosen sequences. The most widespread involves combining zinc-finger units with known specificities (modular assembly). Various selection techniques, using bacteria, yeast or mammal cells have been developed to identify the
489:
The recognized sequences are short, made up of around 3 base pairs, but by combining 6 to 8 zinc fingers whose recognition sites have been characterized, it is possible to obtain specific proteins for sequences of around 20 base pairs. It is therefore possible to control the expression of a specific
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The key to genome editing is creating a DSB at a specific point within the genome. Commonly used restriction enzymes are effective at cutting DNA, but generally recognize and cut at multiple sites. To overcome this challenge and create site-specific DSB, three distinct classes of nucleases have been
330:
is an enzyme that removes DNA by homologous recombination between binding sequences known as Lox-P sites. The Flip-FRT system operates in a similar way, with the Flip recombinase recognising FRT sequences. By crossing an organism containing the recombinase sites flanking the gene of interest with an
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In the future, an important goal of research into genome editing with engineered nucleases must be the improvement of the safety and specificity of the nucleases action. For example, improving the ability to detect off-target events can improve our ability to learn about ways of preventing them. In
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One potential that CRISPR brings with its effectiveness is the application of xenotransplantation. In previous research trials, CRISPR demonstrated the ability to target and eliminate endogenous retroviruses, which reduces the risk of transmitting diseases and reduces immune barriers. Eliminating
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into modifying the genome with engineered nucleases has shown the need for better understanding of the basic recombination and repair machinery of DNA. In the future, a possible method to identify secondary targets would be to capture broken ends from cells expressing the ZFNs and to sequence the
1103:
practice is that which replaces the defective gene with a normal allele at its natural location. This is advantageous over a virally delivered gene as there is no need to include the full coding sequences and regulatory sequences when only a small proportions of the gene needs to be altered as is
854:
Several optimizations need to be made in order to improve editing plant genomes using ZFN-mediated targeting. There is a need for reliable design and subsequent test of the nucleases, the absence of toxicity of the nucleases, the appropriate choice of the plant tissue for targeting, the routes of
439:
Meganucleases, found commonly in microbial species, have the unique property of having very long recognition sequences (>14bp) thus making them naturally very specific. However, there is virtually no chance of finding the exact meganuclease required to act on a chosen specific DNA sequence. To
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Traditionally, mice have been the most common choice for researchers as a host of a disease model. CRISPR can help bridge the gap between this model and human clinical trials by creating transgenic disease models in larger animals such as pigs, dogs, and non-human primates. Using the CRISPR-Cas9
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The methods for scientists and researchers wanting to study genomic diversity and all possible associated phenotypes were very slow, expensive, and inefficient. Prior to this new revolution, researchers would have to do single-gene manipulations and tweak the genome one little section at a time,
647:
of an active nuclease would have potentially dangerous consequences at the genetic and organismal levels, the precision of meganucleases, ZFNs, CRISPR, and TALEN-based fusions has been an active area of research. While variable figures have been reported, ZFNs tend to have more cytotoxicity than
635:
TALE nucleases being the most precise and specific method yields a higher efficiency than the previous two methods. It achieves such efficiency because the DNA-binding element consists of an array of TALE subunits, each of them having the capability of recognizing a specific DNA nucleotide chain
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to overproduce isoprenoid lycopene. It took them about 3 days and just over $ 1,000 in materials. The ease, speed, and cost efficiency in which MAGE can alter genomes can transform how industries approach the manufacturing and production of important compounds in the bioengineering, bioenergy,
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The number of possible targets ZFN can recognized was increased to one in every 140 nucleotides. However, both methods are unpredictable because of their DNA-binding elements affecting each other. As a result, high degrees of expertise and lengthy and costly validations processes are required.
613:
One of the earliest methods of efficiently editing nucleic acids employs nucleobase modifying enzymes directed by nucleic acid guide sequences was first described in the 1990s and has seen resurgence more recently. This method has the advantage that it does not require breaking the genomic DNA
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The heterodimer functioning nucleases would avoid the possibility of unwanted homodimer activity and thus increase specificity of the DSB. Although the nuclease portions of both ZFNs and TALEN constructs have similar properties, the difference between these engineered nucleases is in their DNA
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endonuclease which need to dimerize to cleave the double-strand DNA. The two proteins recognize two DNA sequences that are a few nucleotides apart. Linking the two zinc finger proteins to their respective sequences brings the two FokI domains closer together. FokI requires dimerization to have
464:(ZFN), likely because of more stringent DNA sequence recognition; however, the construction of sequence-specific enzymes for all possible sequences is costly and time-consuming, as one is not benefiting from combinatorial possibilities that methods such as ZFNs and TALEN-based fusions utilize.
91:
Genome editing was pioneered in the 1990s, before the advent of the common current nuclease-based gene editing platforms but its use was limited by low efficiencies of editing. Genome editing with engineered nucleases, i.e. all three major classes of these enzymes—zinc finger nucleases (ZFNs),
639:
CRISPR nucleases have a slightly lower precision when compared to the TALE nucleases. This is caused by the need of having a specific nucleotide at one end in order to produce the guide RNA that CRISPR uses to repair the double-strand break it induces. It has been shown to be the quickest and
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The CRISPR-Cas9 system can be programmed to modulate the population of any bacterial species by targeting clinical genotypes or epidemiological isolates. It can selectively enable the beneficial bacterial species over the harmful ones by eliminating pathogen, which gives it an advantage over
622:
ARCUT stands for artificial restriction DNA cutter, it is a technique developed by
Komiyama. This method uses pseudo-complementary peptide nucleic acid (pcPNA), for identifying cleavage site within the chromosome. Once pcPNA specifies the site, excision is carried out by cerium (CE) and EDTA
799:
Thanks to the parallel development of single-cell transcriptomics, genome editing and new stem cell models we are now entering a scientifically exciting period where functional genetics is no longer restricted to animal models but can be performed directly in human samples. Single-cell gene
1333:
issued a report in
February 2017 giving qualified support to human genome editing. They recommended that clinical trials for genome editing might one day be permitted once answers have been found to safety and efficiency problems "but only for serious conditions under stringent oversight."
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which aims to engineer cells and organisms to perform novel functions, is likely to benefit from the ability of engineered nuclease to add or remove genomic elements and therefore create complex systems. In addition, gene functions can be studied using stem cells with engineered nucleases.
452:
A large bank containing several tens of thousands of protein units has been created. These units can be combined to obtain chimeric meganucleases that recognize the target site, thereby providing research and development tools that meet a wide range of needs (fundamental research, health,
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embryo culture) allows for genome editing directly in fertilised oocytes using synthetic highly specific endonucleases. RNA-guided endonucleases:clustered regularly interspaced short palindromic repeats associated Cas9 (CRISPR/Cas9) are a new tool, further increasing the range of methods
383:
to the flanking sequences of a DSB. This will result in the desired change being inserted at the site of the DSB. While HDR based gene editing is similar to the homologous recombination based gene targeting, the rate of recombination is increased by at least three orders of magnitude.
648:
TALEN methods or RNA-guided nucleases, while TALEN and RNA-guided approaches tend to have the greatest efficiency and fewer off-target effects. Based on the maximum theoretical distance between DNA binding and nuclease activity, TALEN approaches result in the greatest precision.
850:
In addition, TALEN-based genome engineering has been extensively tested and optimized for use in plants. TALEN fusions have also been used by a U.S. food ingredient company, Calyxt, to improve the quality of soybean oil products and to increase the storage potential of potatoes
567:
TAL effectors consists of repeated domains, each of which contains a highly conserved sequence of 34 amino acids, and recognize a single DNA nucleotide within the target site. The nuclease can create double strand breaks at the target site that can be repaired by error-prone
54:
that randomly inserts genetic material into a host genome, genome editing targets the insertions to site-specific locations. The basic mechanism involved in genetic manipulations through programmable nucleases is the recognition of target genomic loci and binding of effector
795:
is a genetically modified
Atlantic salmon developed by AquaBounty Technologies. The growth hormone-regulating gene in the Atlantic salmon is replaced with the growth hormone-regulating gene from the Pacific Chinook salmon and a promoter sequence from the ocean pout
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specific meganucelases in a method named rationally designed meganuclease. Another approach involves using computer models to try to predict as accurately as possible the activity of the modified meganucleases and the specificity of the recognized nucleic sequence.
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Antiviral applications for therapies targeting human viruses such as HIV, herpes, and hepatitis B virus are under research. CRISPR can be used to target the virus or the host to disrupt genes encoding the virus cell-surface receptor proteins. In
November 2018,
184:, would be held responsible for any related adverse consequences. A cautionary perspective on the possible blind spots and risks of CRISPR and related biotechnologies has been recently discussed, focusing on the stochastic nature of cellular control processes.
712:
As of 2012 efficient genome editing had been developed for a wide range of experimental systems ranging from plants to animals, often beyond clinical interest, and was becoming a standard experimental strategy in research labs. The recent generation of rat,
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to protect against viruses. They consist of short sequences that originate from viral genomes and have been incorporated into the bacterial genome. Cas (CRISPR associated proteins) process these sequences and cut matching viral DNA sequences. By introducing
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Yaskowiak, Edward S.; Shears, Margaret A.; Agarwal-Mawal, Alka; Fletcher, Garth L. (2006). "Characterization and multi-generational stability of the growth hormone transgene (EO-1α) responsible for enhanced growth rates in
Atlantic Salmon".
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strands, and thus avoids the random insertion and deletions associated with DNA strand breakage. It is only appropriate for precise editing requiring single nucleotide changes and has found to be highly efficient for this type of editing.
636:
independent from others, resulting in a higher number of target sites with high precision. New TALE nucleases take about one week and a few hundred dollars to create, with specific expertise in molecular biology and protein engineering.
375:(HDR). NHEJ uses a variety of enzymes to directly join the DNA ends while the more accurate HDR uses a homologous sequence as a template for regeneration of missing DNA sequences at the break point. This can be exploited by creating a
668:
Chemically combined, synthetic single-stranded DNA (ssDNA) and a pool of oligionucleotides are introduced at targeted areas of the cell thereby creating genetic modifications. The cyclical process involves transformation of ssDNA (by
1122:
Extensive research has been done in cells and animals using CRISPR-Cas9 to attempt to correct genetic mutations which cause genetic diseases such as Down syndrome, spina bifida, anencephaly, and Turner and
Klinefelter syndromes.
240:
within an organism genome. It has also enabled the editing of specific sequences within a genome as well as reduced off target effects. This could be used for research purposes, by targeting mutations to specific genes, and in
270:(HR). By creating DNA constructs that contain a template that matches the targeted genome sequence it is possible that the HR processes within the cell will insert the construct at the desired location. Using this method on
201:
In
February 2020, a US trial safely showed CRISPR gene editing on 3 cancer patients. In 2020 Sicilian Rouge High GABA, a tomato that makes more of an amino acid said to promote relaxation, was approved for sale in Japan.
1234:
addition, zinc-fingers used in ZFNs are seldom completely specific, and some may cause a toxic reaction. However, the toxicity has been reported to be reduced by modifications done on the cleavage domain of the ZFN.
2022:
Altae-Tran, Han; Kannan, Soumya; Demircioglu, F. Esra; Oshiro, Rachel; Nety, Suchita P.; McKay, Luke J.; Dlakić, Mensur; Inskeep, William P.; Makarova, Kira S.; Macrae, Rhiannon K.; Koonin, Eugene V. (2021-10-01).
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Arnould S, Chames P, Perez C, Lacroix E, Duclert A, Epinat JC, et al. (January 2006). "Engineering of large numbers of highly specific homing endonucleases that induce recombination on novel DNA targets".
1302:. According to a September 2016 report by the Nuffield Council on Bioethics in the future it may be possible to enhance people with genes from other organisms or wholly synthetic genes to for example improve
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In particular CRISPR/Cas9 engineered endonucleases allows the use of multiple guide RNAs for simultaneous
Knockouts (KO) in one step by cytoplasmic direct injection (CDI) on mammalian zygotes.
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was awarded to Mario Capecchi, Martin Evans and Oliver Smithies "for their discoveries of principles for introducing specific gene modifications in mice by the use of embryonic stem cells."
2610:
Redondo P, Prieto J, Muñoz IG, Alibés A, Stricher F, Serrano L, et al. (November 2008). "Molecular basis of xeroderma pigmentosum group C DNA recognition by engineered meganucleases".
2861:"Zinc finger nucleases targeting the glucocorticoid receptor allow IL-13 zetakine transgenic CTLs to kill glioblastoma cells in vivo in the presence of immunosuppressing glucocorticoids"
1069:
3966:
Shukla VK, Doyon Y, Miller JC, DeKelver RC, Moehle EA, Worden SE, et al. (May 2009). "Precise genome modification in the crop species Zea mays using zinc-finger nucleases".
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The method generally adopted for this involves associating two DNA binding proteins – each containing 3 to 6 specifically chosen zinc fingers – with the catalytic domain of the
1249:
Genome editing occurs also as a natural process without artificial genetic engineering. The agents that are competent to edit genetic codes are viruses or subviral RNA-agents.
428:
family which are characterized by their capacity to recognize and cut large DNA sequences (from 14 to 40 base pairs). The most widespread and best known meganucleases are the
524:
are research and development tools that have already been used to modify a range of genomes, in particular by the laboratories in the Zinc Finger Consortium. The US company
4984:
575:
TALEN constructs are used in a similar way to designed zinc finger nucleases, and have three advantages in targeted mutagenesis: (1) DNA binding specificity is higher, (2)
453:
agriculture, industry, energy, etc.) These include the industrial-scale production of two meganucleases able to cleave the human XPC gene; mutations in this gene result in
683:
to produce five times the normal amount of lycopene, an antioxidant normally found in tomato seeds and linked to anti-cancer properties. They applied MAGE to optimize the
2707:
Rebar EJ, Huang Y, Hickey R, Nath AK, Meoli D, Nath S, et al. (December 2002). "Induction of angiogenesis in a mouse model using engineered transcription factors".
228:
as method of introducing new genetic elements into organisms has been around since the 1970s. One drawback of this technology has been the random nature with which the
5501:
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often the case. The expression of the partially replaced genes is also more consistent with normal cell biology than full genes that are carried by viral vectors.
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patterns. In recognition of their discovery of how homologous recombination can be used to introduce genetic modifications in mice through embryonic stem cells,
498:
nuclease activity and this means the specificity increases dramatically as each nuclease partner would recognize a unique DNA sequence. To enhance this effect,
660:
Synthetic DNA is repeatedly introduced at multiple targeted areas of the chromosome and/or loci and then is replicated producing cells with/without mutations.
776:
The combination of recent discoveries in genetic engineering, particularly gene editing and the latest improvement in bovine reproduction technologies (e.g.
5009:
4324:"ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy"
1997:
1298:
notes that "the new technologies with genome editing will allow it to be used on individuals (...) to have (...) healthier children" –
1166:, the vector for malaria. This technique has further implications in eradicating other vector borne diseases such as yellow fever, dengue, and Zika.
2992:"An improved method for TAL effectors DNA-binding sites prediction reveals functional convergence in TAL repertoires of Xanthomonas oryzae strains"
4428:
1385:, that could affect humans. Furthermore, there are additional concerns about the ecological risks of releasing gene drives into wild populations.
5305:"The mousepox experience. An interview with Ronald Jackson and Ian Ramshaw on dual-use research. Interview by Michael J. Selgelid and Lorna Weir"
556:
406:
236:, which can impair or alter other genes within the organism. Although, several methods have been discovered which target the inserted genes to
116:
3457:
Gallagher RR, Li Z, Lewis AO, Isaacs FJ (October 2014). "Rapid editing and evolution of bacterial genomes using libraries of synthetic DNA".
3302:"Genome-Editing Technologies: Concept, Pros, and Cons of Various Genome-Editing Techniques and Bioethical Concerns for Clinical Application"
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containing Cas genes and specifically constructed CRISPRs into eukaryotic cells, the eukaryotic genome can be cut at any desired position.
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2096:
1076:
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245:. By inserting a functional gene into an organism and targeting it to replace the defective one it could be possible to cure certain
536:
for therapeutic purposes. Modified T lymphocytes are currently undergoing phase I clinical trials to treat a type of brain tumor (
457:, a severe monogenic disorder that predisposes the patients to skin cancer and burns whenever their skin is exposed to UV rays.
5427:"WHO launches global registry on human genome editing." PharmaBiz, 31 Aug. 2019. Gale General OneFile, Accessed 27 Apr. 2020.
2816:
Urnov FD, Rebar EJ, Holmes MC, Zhang HS, Gregory PD (September 2010). "Genome editing with engineered zinc finger nucleases".
1190:, had been born a few weeks earlier. He said that the girls still carried functional copies of CCR5 along with disabled CCR5 (
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1973:
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Plants, animals and human genes that are successfully targeted using ZFN, which demonstrates the generality of this approach
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576:
315:
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in an 11-month old child in 2015. Modified donor T cells were engineered to attack the leukemia cells, to be resistant to
882:
for plant application. To improve Cas9 delivery in live plants, viruses are being used more effective transgene delivery.
4728:
1822:
5353:
5097:
4648:
1924:
Cheong KH, Koh JM, Jones MC (July 2019). "Black Swans of CRISPR: Stochasticity and Complexity of Genetic Regulation".
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4567:"Ascending Dose Study of Genome Editing by the Zinc Finger Nuclease (ZFN) Therapeutic SB-913 in Subjects With MPS II"
1735:
23:
The different generations of nucleases used for genome editing and the DNA repair pathways used to modify target DNA.
2894:"Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo"
314:
If a vital gene is knocked out it can prove lethal to the organism. In order to study the function of these genes
76:
4600:"A CRISPR-Cas9 gene drive system targeting female reproduction in the malaria mosquito vector Anopheles gambiae"
2123:"Chapter 8.5: Gene Replacement and Transgenic Animals: DNA Is Transferred into Eukaryotic Cells in Various Ways"
596:(Clustered Regularly Interspaced Short Palindromic Repeats) are genetic elements that bacteria use as a kind of
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1655:
684:
51:
5205:
1718:
Tan WS, Carlson DF, Walton MW, Fahrenkrug SC, Hackett PB (2012). "Precision Editing of Large Animal Genomes".
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3744:"The I-CreI meganuclease and its engineered derivatives: applications from cell modification to gene therapy"
1441:
1358:
4460:
Couzin-Frankel J (November 2015). "CANCER IMMUNOTHERAPY. Baby's leukemia recedes after novel cell therapy".
4279:
Paul JW, Qi Y (July 2016). "CRISPR/Cas9 for plant genome editing: accomplishments, problems and prospects".
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virus that would cause infertility as the provided sensitive information could lead to the manufacture of
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that explored the potential control of mice, a major pest in Australia, by infecting them with an altered
1314:
has compiled a list of potential genetic modifications for possibly advantageous traits such as less need
1194:) and were still vulnerable to HIV. The work was widely condemned as unethical, dangerous, and premature.
1361:, the simplicity and low cost of tools to edit the genetic code will allow amateurs – or "
2413:
Seligman LM, Chisholm KM, Chevalier BS, Chadsey MS, Edwards ST, Savage JH, Veillet AL (September 2002).
2201:
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Barrangou R, Doudna JA (September 2016). "Applications of CRISPR technologies in research and beyond".
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1318:, cognition-related changes that protect against Alzheimer's disease, disease resistances and enhanced
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376:
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209:(not the rest of the UK) planned to remove restrictions on gene-edited plants and animals, moving from
92:
transcription activator-like effector nucleases (TALENs) and engineered meganucleases—were selected by
80:
4757:"Variability in Genome Editing Outcomes: Challenges for Research Reproducibility and Clinical Safety"
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146:
72:
5122:
4700:
2990:
Pérez-Quintero AL, Rodriguez-R LM, Dereeper A, López C, Koebnik R, Szurek B, Cunnac S (2013-07-15).
2025:"The widespread IS200/IS605 transposon family encodes diverse programmable RNA-guided endonucleases"
3503:
McMahon MA, Rahdar M, Porteus M (December 2011). "Gene editing: not just for translation anymore".
1401:
745:
372:
267:
150:
64:
5379:
696:
biomedical engineering, synthetic biology, pharmaceutical, agricultural, and chemical industries.
5548:
4132:"Improved soybean oil quality by targeted mutagenesis of the fatty acid desaturase 2 gene family"
1261:
these problems improves donor organ function, which brings this application closer to a reality.
1202:
980:
913:
656:
188:
3058:
2563:"Computational reprogramming of homing endonuclease specificity at multiple adjacent base pairs"
4598:
Hammond A, Galizi R, Kyrou K, Simoni A, Siniscalchi C, Katsanos D, et al. (January 2016).
4322:
Monga, Isha; Qureshi, Abid; Thakur, Nishant; Gupta, Amit Kumar; Kumar, Manoj (September 2017).
3845:
Zhang F, Maeder ML, Unger-Wallace E, Hoshaw JP, Reyon D, Christian M, et al. (June 2010).
3604:
1405:
1362:
1050:
1045:
195:
3141:"To cleave or not to cleave: therapeutic gene editing with and without programmable nucleases"
2366:"A combinatorial approach to create artificial homing endonucleases cleaving chosen sequences"
1381:
who might use the knowledge to create vaccine resistant strains of other pox viruses, such as
1315:
1295:
1019:
1004:
521:
515:
483:
323:
319:
19:
5404:
2541:
Rationally-designed meganucleases with altered sequence specificity and DNA-binding affinity
1264:
In plants, genome editing is seen as a viable solution to the conservation of biodiversity.
356:
4918:
4228:
3975:
3917:
3858:
3801:
3559:
3196:
3185:"Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage"
3093:
3003:
2763:
2619:
2036:
1198:
1147:
1131:
1127:
951:
525:
461:
402:
364:
336:
138:
112:
5466:
4905:
Johnson JA, Altwegg R, Evans DM, Ewen JG, Gordon IJ, Pettorelli N, Young JK (2016-04-01).
4539:
8:
5521:
4171:
Clasen BM, Stoddard TJ, Luo S, Demorest ZL, Li J, Cedrone F, et al. (January 2016).
3847:"High frequency targeted mutagenesis in Arabidopsis thaliana using zinc finger nucleases"
1848:
1366:
1014:
871:
833:
792:
588:
433:
332:
271:
225:
181:
60:
39:
4922:
4232:
4130:
Haun W, Coffman A, Clasen BM, Demorest ZL, Lowy A, Ray E, et al. (September 2014).
3979:
3921:
3862:
3805:
3742:
Arnould S, Delenda C, Grizot S, Desseaux C, Pâques F, Silva GH, Smith J (January 2011).
3563:
3200:
3097:
3007:
2767:
2623:
2040:
5454:
5329:
5304:
4942:
4882:
4857:
4830:
4805:
4781:
4756:
4624:
4599:
4571:
4520:
4404:
4379:
4350:
4323:
4304:
4251:
4216:
4173:"Improving cold storage and processing traits in potato through targeted gene knockout"
4051:
4018:
3999:
3940:
3905:
3881:
3846:
3822:
3789:
3683:
3632:
3580:
3547:
3528:
3482:
3432:
3407:
Kim H, Kim JS (May 2014). "A guide to genome engineering with programmable nucleases".
3389:
3334:
3301:
3282:
3217:
3184:
3026:
2991:
2967:
2942:
2918:
2893:
2841:
2732:
2689:
2643:
2587:
2562:
2390:
2365:
2341:
2289:
2078:
2065:
2024:
1949:
1899:
1746:
1727:
1695:
1670:
1596:
1544:
1489:
974:
756:
56:
4100:
3906:"Site-directed mutagenesis in Arabidopsis using custom-designed zinc finger nucleases"
2877:
2860:
2561:
Ashworth J, Taylor GK, Havranek JJ, Quadri SA, Stoddard BL, Baker D (September 2010).
2480:
2463:
2462:
Chevalier BS, Kortemme T, Chadsey MS, Baker D, Monnat RJ, Stoddard BL (October 2002).
2439:
2414:
870:
is introduced directly into the plant genome by a T4SS mechanism. Cas9 and gRNA-based
460:
Meganucleases have the benefit of causing less toxicity in cells than methods such as
262:
Early methods to target genes to certain sites within a genome of an organism (called
5458:
5334:
5181:
4934:
4887:
4835:
4786:
4656:
4629:
4512:
4477:
4436:
4409:
4355:
4296:
4256:
4194:
4153:
4056:
3991:
3945:
3886:
3827:
3788:
Townsend JA, Wright DA, Winfrey RJ, Fu F, Maeder ML, Joung JK, Voytas DF (May 2009).
3765:
3724:
3675:
3636:
3624:
3585:
3520:
3474:
3424:
3381:
3339:
3321:
3286:
3274:
3266:
3222:
3162:
3121:
3116:
3081:
3031:
2972:
2923:
2845:
2833:
2791:
2786:
2751:
2724:
2681:
2635:
2592:
2521:
2485:
2444:
2395:
2333:
2281:
2246:
2241:
2224:
2180:
2134:
2127:
2082:
2070:
2052:
1953:
1941:
1903:
1891:
1875:
1792:
1751:
1731:
1700:
1636:
1588:
1536:
1528:
1493:
1431:
1374:
1291:
1009:
897:
727:
597:
380:
131:
100:
4946:
4524:
4508:
3687:
3486:
3393:
2736:
2693:
2345:
2293:
1548:
1322:
abilities along with some of the associated studies and potential negative effects.
840:
editing to inactivate the endogenous banana streak virus in the B genome of banana (
409:), meganucleases and the clustered regularly interspaced short palindromic repeats (
5446:
5324:
5316:
4926:
4877:
4869:
4825:
4817:
4776:
4768:
4619:
4611:
4504:
4469:
4399:
4391:
4345:
4335:
4308:
4288:
4246:
4236:
4184:
4143:
4087:
4046:
4038:
4003:
3983:
3935:
3925:
3876:
3866:
3817:
3809:
3790:"High-frequency modification of plant genes using engineered zinc-finger nucleases"
3755:
3714:
3667:
3616:
3575:
3567:
3532:
3512:
3466:
3436:
3416:
3373:
3329:
3313:
3256:
3212:
3204:
3152:
3111:
3101:
3021:
3011:
2962:
2954:
2913:
2905:
2872:
2825:
2781:
2771:
2716:
2673:
2647:
2627:
2582:
2574:
2539:
2513:
2475:
2434:
2426:
2385:
2377:
2323:
2273:
2236:
2170:
2159:"From Gene Targeting to Genome Editing: Transgenic animals applications and beyond"
2060:
2044:
1933:
1883:
1782:
1741:
1723:
1690:
1682:
1626:
1600:
1580:
1520:
1481:
1347:
1269:
1178:
announced that he had edited two human embryos, to attempt to disable the gene for
1107:
The first clinical use of TALEN-based genome editing was in the treatment of CD19+
679:
479:
246:
237:
191:
94:
4566:
2958:
2364:
Smith J, Grizot S, Arnould S, Duclert A, Epinat JC, Chames P, et al. (2006).
2175:
2158:
808:
4473:
4092:
4075:
3242:
3016:
2122:
1409:
1299:
1143:
960:
670:
528:
uses zinc finger nucleases to carry out research into the genetic engineering of
327:
299:
287:
275:
5437:
Saurabh S (March 2021). "Genome Editing: Revolutionizing the Crop Improvement".
5147:
4772:
2892:
Holt N, Wang J, Kim K, Friedman G, Wang X, Taupin V, et al. (August 2010).
1472:
Saurabh S (March 2021). "Genome Editing: Revolutionizing the Crop Improvement".
396:
Groups of engineered nucleases. Matching colors signify DNA recognition patterns
141:(DSBs) at desired locations in the genome. The induced double-strand breaks are
5450:
4873:
4806:"Applications of CRISPR/Cas9 for Gene Editing in Hereditary Movement Disorders"
4221:
Proceedings of the National Academy of Sciences of the United States of America
3910:
Proceedings of the National Academy of Sciences of the United States of America
3851:
Proceedings of the National Academy of Sciences of the United States of America
3620:
3571:
3317:
3086:
Proceedings of the National Academy of Sciences of the United States of America
2756:
Proceedings of the National Academy of Sciences of the United States of America
1887:
1485:
1307:
291:
263:
210:
4985:"How DIY bio-hackers are changing the conversation around genetic engineering"
4292:
4042:
3719:
3702:
3671:
3261:
3245:"APOBECs orchestrate genomic and epigenomic editing across health and disease"
3244:
2517:
2464:"Design, activity, and structure of a highly specific artificial endonuclease"
2277:
2157:
Rocha-Martins M, Cavalheiro GR, Matos-Rodrigues GE, Martins RA (August 2015).
1568:
1524:
5542:
5502:"Scientific split - the human genome breakthrough dividing former colleagues"
5185:
4938:
4660:
4440:
3760:
3743:
3325:
3270:
2156:
2056:
1998:"US Trial Shows 3 Cancer Patients Had Their Genomes Altered Safely by CRISPR"
1876:"China set to introduce gene-editing regulation following CRISPR-baby furore"
1532:
1436:
1287:
1222:
1206:
1197:
In January 2019, scientists in China reported the creation of five identical
1187:
421:
283:
279:
4241:
3930:
3871:
3106:
2121:
Lodish H, Berk A, Zipursky SL, Matsudaira P, Baltimore D, Darnell J (2000).
2048:
704:
119:(TALEN), and the clustered regularly interspaced short palindromic repeats (
5338:
5320:
4891:
4839:
4790:
4682:"Amid uproar, Chinese scientist defends creating gene-edited babies - STAT"
4633:
4516:
4481:
4413:
4359:
4300:
4260:
4198:
4157:
4060:
4017:
Tripathi JN, Ntui VO, Ron M, Muiruri SK, Britt A, Tripathi L (2019-01-31).
3995:
3949:
3890:
3831:
3769:
3728:
3679:
3628:
3589:
3524:
3478:
3470:
3428:
3385:
3343:
3278:
3226:
3166:
3035:
2976:
2927:
2837:
2776:
2728:
2685:
2639:
2596:
2525:
2489:
2448:
2399:
2337:
2285:
2264:
Stoddard BL (February 2005). "Homing endonuclease structure and function".
2184:
2074:
1945:
1937:
1895:
1796:
1755:
1704:
1640:
1540:
1508:
1378:
1303:
1238:
1100:
946:
867:
841:
817:
560:
537:
533:
425:
401:
discovered and bioengineered to date. These are the Zinc finger nucleases (
295:
242:
177:
108:
4340:
3125:
2795:
2752:"Hybrid restriction enzymes: zinc finger fusions to Fok I cleavage domain"
2250:
1787:
1770:
1592:
1507:
Bak, Rasmus O.; Gomez-Ospina, Natalia; Porteus, Matthew H. (August 2018).
1225:. The monkey clones were made in order to study several medical diseases.
4705:
2578:
2430:
2381:
1426:
1421:
1201:
gene-edited monkeys, using the same cloning technique that was used with
1112:
1024:
995:
856:
837:
476:
441:
214:
4962:"Geneticists Are Concerned Transhumanists Will Use CRISPR on Themselves"
4395:
3987:
3813:
3243:
Cervantes-Gracia K, Gramalla-Schmitz A, Weischedel J, Chahwan R (2021).
3208:
3157:
3140:
2631:
2097:"New programmable gene editing proteins found outside of CRISPR systems"
1686:
1584:
4821:
4495:
Mentis AF (December 2016). "Epigenomic engineering for Down syndrome".
3548:"Embryonic POU5F1 is Required for Expanded Bovine Blastocyst Formation"
3516:
2720:
2677:
2328:
2311:
1631:
1614:
1265:
1218:
1175:
1159:
875:
761:
751:
529:
392:
165:
142:
4930:
4380:"Progress and prospects: zinc-finger nucleases as gene therapy agents"
4189:
4172:
4148:
4131:
2989:
2415:"Mutations altering the cleavage specificity of a homing endonuclease"
367:(DSB) repair mechanics. There are two major pathways that repair DSB;
98:
as the 2011 Method of the Year. The CRISPR-Cas system was selected by
4615:
3377:
2909:
1253:
will also be at work correcting the DSB with lower mutational rates.
1191:
986:
714:
548:
4907:"Is there a future for genome-editing technologies in conservation?"
4858:"Development and applications of CRISPR-Cas9 for genome engineering"
3656:
3420:
2829:
608:
4076:"Recent developments in genome editing for potential use in plants"
1823:"Rewriting the book of life: a new era in precision genome editing"
1382:
1370:
1319:
918:
626:
429:
154:
134:
579:
are lower, and (3) construction of DNA-binding domains is easier.
198:, which costs US and European pig farmers $ 2.6 billion annually.
164:
reported, in light of the purported creation by Chinese scientist
4733:
4544:
2943:"ZFN, TALEN, and CRISPR/Cas-based methods for genome engineering"
2225:"Genetic manipulation of genomes with rare-cutting endonucleases"
2021:
722:
651:
602:
206:
5282:"Top U.S. Intelligence Official Calls Gene Editing a WMD Threat"
5123:"George Church told us why he's listing "superhuman" gene hacks"
2412:
789:
a more sustainable environment and better welfare for the fish.
734:
Listed below are some specific tasks this method can carry out:
137:, or "molecular scissors". These nucleases create site-specific
5506:
5096:. Nuffield Council on Bioethics. September 2016. Archived from
4755:
Teboul L, Herault Y, Wells S, Qasim W, Pavlovic G (June 2020).
1210:
941:
593:
410:
233:
120:
47:
5232:"Worldwide Threat Assessment of the US Intelligence Community"
4540:"Tests suggest scientists achieved 1st 'in body' gene editing"
3844:
3701:
Ortega NM, Winblad N, Plaza Reyes A, Lanner F (October 2018).
3700:
2461:
1451:
718:
502:
have been engineered that can only function as heterodimers.
432:
in the LAGLIDADG family, which owe their name to a conserved
161:
5059:"Experts warn home 'gene editing' kits pose risk to society"
4729:"China's Latest Cloned-Monkey Experiment Is an Ethical Mess"
4429:"A Cell Therapy Untested in Humans Saves a Baby With Cancer"
3741:
2560:
2120:
1974:"U.K. set to loosen rules for gene-edited crops and animals"
1671:"Genome-scale engineering for systems and synthetic biology"
1344:
Worldwide Threat Assessment of the US Intelligence Community
379:
with the desired genetic elements within a sequence that is
176:), the drafting of regulations that anyone manipulating the
107:
As of 2015 four families of engineered nucleases were used:
1346:
statement United States Director of National Intelligence,
1214:
1179:
507:
499:
494:
124:
68:
3183:
Komor AC, Kim YB, Packer MS, Zuris JA, Liu DR (May 2016).
1717:
1146:. Clinical trials by Sangamo involving gene editing using
677:
in 2009, where Church and colleagues were able to program
623:(chemical mixture), which performs the splicing function.
4170:
4129:
3965:
3545:
3139:
Woolf TM, Gurumurthy CB, Boyce F, Kmiec EB (April 2017).
3138:
3082:"Toward the therapeutic editing of mutated RNA sequences"
2502:
2363:
1183:
1139:
363:
A common form of Genome editing relies on the concept of
229:
127:) system. Nine genome editors were available as of 2017.
43:
4597:
2609:
771:
4904:
4754:
4649:"Mutant mosquitoes: Can gene editing kill off malaria?"
4321:
3787:
3605:"Application of genome editing in aquatic farm animals"
3546:
Daigneault BW, Rajput S, Smith GW, Ross PJ (May 2018).
1268:
are a potential tool to alter the reproductive rate of
803:
4016:
3456:
2554:
1569:"Therapeutic repair of mutated nucleic acid sequences"
1506:
1412:
for "the development of a method for genome editing".
1221:
in creating the first ever gene-modified human babies
862:
A common delivery method for CRISPR/Cas9 in plants is
5174:"Human Gene Editing Receives Science Panel's Support"
3293:
2815:
117:
transcription activator-like effector-based nucleases
5275:
5273:
4027:
spp. overcomes a major challenge in banana breeding"
3502:
3079:
2749:
2706:
847:) to overcome a major challenge in banana breeding.
563:, DNA-binding proteins excreted by plant pathogenic
405:), transcription-activator like effector nucleases (
5257:"Genome editing: Is it a national security threat?"
4698:
3182:
2891:
1272:, although there are significant associated risks.
1246:productions due to their precision and efficiency.
812:
Overview of GEEN workflow and editing possibilities
424:, discovered in the late 1980s, are enzymes in the
318:(SSR) were used. The two most common types are the
3903:
2664:Baker M (January 2012). "Gene-editing nucleases".
2312:"Primer: genome editing with engineered nucleases"
2126:
1775:The International Journal of Developmental Biology
1653:
1126:In February 2019, medical scientists working with
130:In 2018, the common methods for such editing used
46:is inserted, deleted, modified or replaced in the
5483:"Customized Human Genes: New Promises and Perils"
5270:
3452:
3450:
3448:
3446:
3359:
3357:
3355:
3353:
3080:Woolf TM, Chase JM, Stinchcomb DT (August 1995).
2940:
2750:Kim YG, Cha J, Chandrasegaran S (February 1996).
2305:
2303:
1294:. Australian biologist and Professor of Genetics
609:Editing by nucleobase modification (Base editing)
194:engineered pigs resistant to a virus that causes
5540:
3703:"Functional genetics of early human development"
2202:"The Nobel Prize in Physiology or Medicine 2007"
1656:"Breakthrough of the Year: CRISPR makes the cut"
627:Precision and efficiency of engineered nucleases
5052:
5050:
3783:
3781:
3779:
3498:
3496:
3363:
2152:
2150:
1816:
1814:
1812:
1810:
1808:
1806:
1242:flanking DNA using high-throughput sequencing.
557:Transcription activator-like effector nucleases
331:organism that express the SSR under control of
5302:
5206:"Scientists OK genetically engineering babies"
4855:
4459:
4217:"Breaking news: plants mutate right on target"
3443:
3350:
2300:
1923:
1186:uses to enter cells. He said that twin girls,
726:therapy in humans. For instance, the field of
652:Multiplex Automated Genomic Engineering (MAGE)
4701:"Gene-edited disease monkeys cloned in China"
4315:
3707:Current Opinion in Genetics & Development
2811:
2809:
2807:
2805:
1849:"The future of genetic codes and BRAIN codes"
1162:to modify genes associated with sterility in
1070:
859:, and a reliable detection of mutated cases.
359:and genome editing using CRISPR-Cas nucleases
347:
196:porcine reproductive and respiratory syndrome
5085:
5083:
5081:
5079:
5047:
4720:
4692:
4591:
3897:
3838:
3776:
3493:
3236:
2700:
2455:
2147:
1867:
1803:
1768:
1357:According to a September 2016 report by the
1228:
4851:
4849:
4531:
3748:Protein Engineering, Design & Selection
2941:Gaj T, Gersbach CA, Barbas CF (July 2013).
2743:
2216:
2133:(4th ed.). W. H. Freeman and Company.
1820:
1762:
1607:
1290:see genome editing as a potential tool for
257:
4726:
4373:
4371:
4369:
4214:
3904:Osakabe K, Osakabe Y, Toki S (June 2010).
2802:
1771:"Gene targeting in plants: 25 years later"
1668:
1077:
1063:
855:induction of enzyme activity, the lack of
5467:"Special Issue on Human Germline Editing"
5354:"Australians Create a Deadly Mouse Virus"
5328:
5254:
5076:
4881:
4829:
4803:
4780:
4623:
4559:
4537:
4403:
4349:
4339:
4250:
4240:
4210:
4208:
4188:
4147:
4091:
4050:
3961:
3959:
3939:
3929:
3880:
3870:
3821:
3759:
3718:
3602:
3579:
3333:
3260:
3216:
3156:
3115:
3105:
3025:
3015:
2966:
2917:
2876:
2785:
2775:
2586:
2479:
2438:
2389:
2327:
2240:
2196:
2194:
2174:
2064:
1873:
1786:
1745:
1694:
1630:
4959:
4856:Hsu PD, Lander ES, Zhang F (June 2014).
4846:
4646:
4106:
2659:
2657:
2359:
2357:
2355:
2309:
2263:
2163:Anais da Academia Brasileira de Ciências
1971:
807:
703:
655:
547:
467:
391:
351:
309:
18:
5436:
5377:
5229:
4699:Science China Press (23 January 2019).
4426:
4377:
4366:
4073:
1654:Science News Staff (17 December 2015).
1471:
1454:, a ssDNA-guided Argonaute endonuclease
1153:
387:
5541:
5499:
5380:"Lab creates killer virus by accident"
5171:
5056:
4804:Im W, Moon J, Kim M (September 2016).
4679:
4497:Neuroscience and Biobehavioral Reviews
4494:
4278:
4205:
3956:
3406:
2191:
1846:
1395:Nobel Prize for Physiology or Medicine
1350:, named genome editing as a potential
1205:– the first ever cloned monkeys - and
304:Nobel Prize for Physiology or Medicine
5351:
5303:Jackson R, Ramshaw I (January 2010).
4982:
4274:
4272:
4270:
3178:
3176:
3048:
2663:
2654:
2352:
2222:
1967:
1965:
1963:
1566:
1134:, announced the first ever "in body"
924:Registry of Standard Biological Parts
772:Targeted gene modification in animals
552:General overview of the TALEN process
5279:
5030:
3299:
2858:
1562:
1560:
1558:
1275:
804:Targeted gene modification in plants
5411:from the original on 7 October 2020
5405:"The Nobel Prize in Chemistry 2020"
5091:"Genome editing: an ethical review"
4019:"CRISPR/Cas9 editing of endogenous
3300:Khan, Sikandar Hayat (2019-06-07).
3042:
1117:detection by the host immune system
50:of a living organism. Unlike early
13:
5430:
4640:
4267:
4109:"These Are Not Your Father's GMOs"
3173:
1960:
1728:10.1016/B978-0-12-404742-6.00002-8
1182:, which codes for a receptor that
1158:Researchers have used CRISPR-Cas9
104:as 2015 Breakthrough of the Year.
75:), and the repair of DSBs through
14:
5560:
5012:. Pew Research Center. 2016-07-26
4727:Mandelbaum RF (23 January 2019).
4577:U.S. National Library of Medicine
1555:
540:) and in the fight against AIDS.
252:
180:by gene-editing techniques, like
3306:Molecular Therapy. Nucleic Acids
1722:. Vol. 80. pp. 37–97.
416:
5439:Plant Molecular Biology Reporte
5397:
5371:
5345:
5296:
5248:
5223:
5198:
5165:
5140:
5115:
5024:
5002:
4976:
4953:
4898:
4797:
4748:
4673:
4538:Marchione M (7 February 2019).
4509:10.1016/j.neubiorev.2016.09.012
4488:
4453:
4420:
4164:
4123:
4107:Regalado A (19 December 2017).
4067:
4010:
3735:
3694:
3650:
3596:
3539:
3400:
3132:
3073:
2983:
2934:
2885:
2852:
2603:
2532:
2496:
2406:
2266:Quarterly Reviews of Biophysics
2257:
2114:
2089:
2015:
1990:
1917:
1840:
1474:Plant Molecular Biology Reporte
1094:
890:Part of a series of articles on
699:
282:. It has also been possible to
77:homology-directed recombination
5230:Clapper JR (9 February 2016).
5057:Sample I (30 September 2016).
5033:"Engineering the Perfect Baby"
4215:Puchta H, Hohn B (June 2010).
3145:Nature Reviews. Drug Discovery
1711:
1662:
1647:
1509:"Gene Editing on Center Stage"
1500:
1465:
1388:
52:genetic engineering techniques
1:
5378:Radford T (10 January 2001).
4810:Journal of Movement Disorders
4680:Begley S (28 November 2018).
2959:10.1016/j.tibtech.2013.04.004
2878:10.1016/S1525-0016(16)39437-0
2481:10.1016/S1097-2765(02)00690-1
2176:10.1590/0001-3765201520140710
1972:Stokstad, Erik (2021-05-26).
1458:
1442:Transposons as a genetic tool
1359:Nuffield Council on Bioethics
905:Synthetic biological circuits
220:
217:, and guided by small ωRNAs.
5352:Broad WJ (23 January 2001).
4474:10.1126/science.350.6262.731
3049:Young S (11 February 2014).
3017:10.1371/journal.pone.0068464
2859:Reik A, et al. (2008).
2506:Journal of Molecular Biology
2242:10.1016/0168-9525(96)10019-6
1847:Church G (9 February 2017).
1331:National Academy of Medicine
1327:National Academy of Sciences
1217:technique allegedly used by
1209:, and the same gene-editing
1170:broad-spectrum antibiotics.
1109:acute lymphoblastic leukemia
153:(HR), resulting in targeted
63:(DSBs) in target DNA by the
7:
4773:10.1016/j.ymthe.2020.03.015
4378:Carroll D (November 2008).
4177:Plant Biotechnology Journal
4136:Plant Biotechnology Journal
2310:de Souza N (January 2012).
1769:Puchta H, Fauser F (2013).
1669:Esvelt KM, Wang HH (2013).
1415:
1089:
878:, which are transformed in
767:Targeted transgene addition
691:(DXP) metabolic pathway in
357:dsDNA-break repair pathways
232:is inserted into the hosts
16:Type of genetic engineering
10:
5565:
5500:Connor S (25 April 2014).
5451:10.1007/s11105-021-01286-7
5255:Warmflash D (2016-09-06).
4874:10.1016/j.cell.2014.05.010
4093:10.1093/biohorizons/hzx016
3621:10.1007/s11248-019-00163-0
3572:10.1038/s41598-018-25964-x
3318:10.1016/j.omtn.2019.02.027
1888:10.1038/d41586-019-01580-1
1486:10.1007/s11105-021-01286-7
1447:Germinal choice technology
1352:weapon of mass destruction
1279:
1136:human gene editing therapy
586:
570:non-homologous end-joining
369:non-homologous end joining
348:Double strand break repair
342:
316:site specific recombinases
274:led to the development of
86:
81:non-homologous end joining
5522:"What is genome editing?"
4960:Pearlman A (2015-12-03).
4647:Fletcher M (2018-08-11).
4293:10.1007/s00299-016-1985-z
4043:10.1038/s42003-019-0288-7
3720:10.1016/j.gde.2018.04.005
3672:10.1007/s11248-006-0020-5
3262:10.1016/j.tig.2021.07.003
2871:(Supplement 1): S13–S14.
2518:10.1016/j.jmb.2005.10.065
2278:10.1017/s0033583505004063
1828:. Boston Consulting Group
1675:Molecular Systems Biology
1615:"Method of the Year 2011"
1525:10.1016/j.tig.2018.05.004
1282:Human genetic enhancement
1237:In addition, research by
1229:Prospects and limitations
970:Artificial gene synthesis
750:Study gene function with
582:
446:high throughput screening
440:overcome this challenge,
365:DNA double stranded break
333:tissue specific promoters
174:Lulu and Nana controversy
147:nonhomologous end-joining
65:restriction endonucleases
4427:Pollack A (2015-11-05).
4074:Townson J (2017-01-01).
3603:Wargelius, Anna (2019).
3409:Nature Reviews. Genetics
3312:. Elsevier BV: 326–334.
2818:Nature Reviews. Genetics
1874:Cyranoski D (May 2019).
1402:Nobel Prize in Chemistry
1337:
834:gene expression cassette
746:chromosome rearrangement
617:
543:
532:and the modification of
373:homology directed repair
268:homologous recombination
258:Homologous recombination
170:first gene-edited humans
160:In May 2019, lawyers in
151:homologous recombination
5284:. MIT Technology Review
5172:Harmon A (2017-02-14).
5035:. MIT Technology Review
4242:10.1073/pnas.1006364107
4111:. MIT Technology Review
3931:10.1073/pnas.1000234107
3872:10.1073/pnas.0914991107
3107:10.1073/pnas.92.18.8298
2947:Trends in Biotechnology
2049:10.1126/science.abj6856
1821:Boglioli E, Richard M.
1567:Woolf TM (April 1998).
1203:Zhong Zhong and Hua Hua
981:Mycoplasma laboratorium
914:Synthetic gene database
866:-based transformation.
189:University of Edinburgh
5321:10.1038/embor.2009.270
4031:Communications Biology
3761:10.1093/protein/gzq083
3471:10.1038/nprot.2014.082
2777:10.1073/pnas.93.3.1156
2567:Nucleic Acids Research
2419:Nucleic Acids Research
2370:Nucleic Acids Research
2204:. The Nobel Foundation
2129:Molecular Cell Biology
1938:10.1002/bies.201900032
1625:(1): 1. January 2012.
1406:Emmanuelle Charpentier
1051:Do-it-yourself biology
1046:Open synthetic biology
857:off-target mutagenesis
813:
738:Targeted gene mutation
709:
661:
553:
397:
360:
302:were awarded the 2007
24:
5212:. Reuters. 2017-02-14
4341:10.1534/g3.117.044024
3055:MIT Technology Review
2223:Jasin M (June 1996).
1788:10.1387/ijdb.130194hp
1296:David Andrew Sinclair
1138:to permanently alter
1020:Expanded genetic code
1005:Nucleic acid analogue
816:Genome editing using
811:
707:
689:-xylulose 5-phosphate
659:
551:
522:Zinc finger nucleases
516:transcription factors
484:transcription factors
468:Zinc finger nucleases
455:Xeroderma pigmentosum
395:
355:
337:stages of development
310:Conditional targeting
113:zinc finger nucleases
22:
5407:. Nobel Foundation.
5152:arep.med.harvard.edu
5148:"Protective alleles"
4604:Nature Biotechnology
3615:(Suppl 2): 101–105.
3366:Nature Biotechnology
2898:Nature Biotechnology
2169:(2 Suppl): 1323–48.
1720:Advances in Genetics
1573:Nature Biotechnology
1154:Eradicating diseases
1148:Zinc Finger Nuclease
1142:- in a patient with
1132:Richmond, California
1128:Sangamo Therapeutics
1119:after introduction.
952:Synthetic immunology
872:expression cassettes
830:Arabidopsis thaliana
822:Arabidopsis thaliana
462:Zinc finger nuclease
388:Engineered nucleases
278:with targeted genes
272:embryonic stem cells
139:double-strand breaks
61:double-strand breaks
5487:Scientific American
5103:on 14 November 2016
5010:"Human Enhancement"
4989:The Washington Post
4923:2016AnCon..19...97J
4911:Animal Conservation
4396:10.1038/gt.2008.145
4233:2010PNAS..10711657P
4080:Bioscience Horizons
4023:in the B genome of
4021:banana streak virus
3988:10.1038/nature07992
3980:2009Natur.459..437S
3922:2010PNAS..10712034O
3863:2010PNAS..10712028Z
3814:10.1038/nature07845
3806:2009Natur.459..442T
3660:Transgenic Research
3609:Transgenic Research
3564:2018NatSR...8.7753D
3209:10.1038/nature17946
3201:2016Natur.533..420K
3158:10.1038/nrd.2017.42
3098:1995PNAS...92.8298W
3061:on 15 February 2014
3008:2013PLoSO...868464P
2768:1996PNAS...93.1156K
2632:10.1038/nature07343
2624:2008Natur.456..107R
2041:2021Sci...374...57A
1687:10.1038/msb.2012.66
1585:10.1038/nbt0498-341
1367:Journal of Virology
1150:(ZFN) are ongoing.
1130:, headquartered in
1015:Unnatural base pair
793:AquAdvantage salmon
645:off-target activity
589:CRISPR gene editing
526:Sangamo BioSciences
434:amino acid sequence
226:Genetic engineering
40:genetic engineering
5358:The New York Times
5178:The New York Times
4964:. Vice Motherboard
4822:10.14802/jmd.16029
4572:ClinicalTrials.gov
4433:The New York Times
4281:Plant Cell Reports
3552:Scientific Reports
3517:10.1038/nmeth.1811
2721:10.1038/nm1202-795
2678:10.1038/nmeth.1807
2579:10.1093/nar/gkq283
2431:10.1093/nar/gkf495
2382:10.1093/nar/gkl720
2329:10.1038/nmeth.1848
2229:Trends in Genetics
1632:10.1038/nmeth.1852
1513:Trends in Genetics
1375:biological weapons
975:Synthetic genomics
814:
757:Transgenic animals
710:
662:
577:off-target effects
554:
510:nuclease domains.
398:
361:
57:DNA-binding domain
32:genome engineering
25:
4931:10.1111/acv.12273
4761:Molecular Therapy
4579:. 2 February 2019
4190:10.1111/pbi.12370
4149:10.1111/pbi.12201
3255:(11): 1028–1043.
2140:978-0-7167-3136-8
2004:. 7 February 2020
1432:Epigenome editing
1292:human enhancement
1276:Human enhancement
1087:
1086:
1010:Xeno nucleic acid
898:Synthetic biology
892:
728:synthetic biology
688:
598:acquired immunity
482:occur in several
5556:
5535:
5533:
5532:
5517:
5515:
5514:
5496:
5494:
5493:
5478:
5462:
5421:
5420:
5418:
5416:
5401:
5395:
5394:
5392:
5390:
5375:
5369:
5368:
5366:
5364:
5349:
5343:
5342:
5332:
5300:
5294:
5293:
5291:
5289:
5277:
5268:
5267:
5265:
5263:
5252:
5246:
5245:
5243:
5241:
5236:
5227:
5221:
5220:
5218:
5217:
5202:
5196:
5195:
5193:
5192:
5169:
5163:
5162:
5160:
5158:
5144:
5138:
5137:
5135:
5133:
5119:
5113:
5112:
5110:
5108:
5102:
5095:
5087:
5074:
5073:
5071:
5069:
5054:
5045:
5044:
5042:
5040:
5028:
5022:
5021:
5019:
5017:
5006:
5000:
4999:
4997:
4995:
4980:
4974:
4973:
4971:
4969:
4957:
4951:
4950:
4902:
4896:
4895:
4885:
4868:(6): 1262–1278.
4853:
4844:
4843:
4833:
4801:
4795:
4794:
4784:
4767:(6): 1422–1431.
4752:
4746:
4745:
4743:
4741:
4724:
4718:
4717:
4715:
4713:
4696:
4690:
4689:
4677:
4671:
4670:
4668:
4667:
4644:
4638:
4637:
4627:
4616:10.1038/nbt.3439
4595:
4589:
4588:
4586:
4584:
4563:
4557:
4556:
4554:
4552:
4535:
4529:
4528:
4492:
4486:
4485:
4457:
4451:
4450:
4448:
4447:
4424:
4418:
4417:
4407:
4375:
4364:
4363:
4353:
4343:
4334:(9): 2931–2943.
4319:
4313:
4312:
4276:
4265:
4264:
4254:
4244:
4212:
4203:
4202:
4192:
4168:
4162:
4161:
4151:
4127:
4121:
4120:
4118:
4116:
4104:
4098:
4097:
4095:
4071:
4065:
4064:
4054:
4014:
4008:
4007:
3974:(7245): 437–41.
3963:
3954:
3953:
3943:
3933:
3901:
3895:
3894:
3884:
3874:
3857:(26): 12028–33.
3842:
3836:
3835:
3825:
3785:
3774:
3773:
3763:
3739:
3733:
3732:
3722:
3698:
3692:
3691:
3654:
3648:
3647:
3645:
3643:
3600:
3594:
3593:
3583:
3543:
3537:
3536:
3500:
3491:
3490:
3459:Nature Protocols
3454:
3441:
3440:
3404:
3398:
3397:
3378:10.1038/nbt.3659
3361:
3348:
3347:
3337:
3297:
3291:
3290:
3264:
3240:
3234:
3230:
3220:
3180:
3171:
3170:
3160:
3136:
3130:
3129:
3119:
3109:
3092:(18): 8298–302.
3077:
3071:
3070:
3068:
3066:
3057:. Archived from
3051:"Genome Surgery"
3046:
3040:
3039:
3029:
3019:
2987:
2981:
2980:
2970:
2938:
2932:
2931:
2921:
2910:10.1038/nbt.1663
2889:
2883:
2882:
2880:
2856:
2850:
2849:
2813:
2800:
2799:
2789:
2779:
2747:
2741:
2740:
2704:
2698:
2697:
2661:
2652:
2651:
2618:(7218): 107–11.
2607:
2601:
2600:
2590:
2558:
2552:
2551:
2550:
2549:
2536:
2530:
2529:
2500:
2494:
2493:
2483:
2459:
2453:
2452:
2442:
2410:
2404:
2403:
2393:
2361:
2350:
2349:
2331:
2307:
2298:
2297:
2261:
2255:
2254:
2244:
2220:
2214:
2213:
2211:
2209:
2198:
2189:
2188:
2178:
2154:
2145:
2144:
2132:
2118:
2112:
2111:
2109:
2108:
2093:
2087:
2086:
2068:
2019:
2013:
2012:
2010:
2009:
1994:
1988:
1987:
1985:
1984:
1969:
1958:
1957:
1921:
1915:
1914:
1912:
1910:
1871:
1865:
1864:
1862:
1860:
1844:
1838:
1837:
1835:
1833:
1827:
1818:
1801:
1800:
1790:
1766:
1760:
1759:
1749:
1715:
1709:
1708:
1698:
1666:
1660:
1659:
1651:
1645:
1644:
1634:
1611:
1605:
1604:
1564:
1553:
1552:
1504:
1498:
1497:
1469:
1348:James R. Clapper
1270:invasive species
1079:
1072:
1065:
961:Artificial cells
888:
885:
884:
874:are turned into
693:Escherichia coli
686:
680:Escherichia coli
565:Xanthomanos app.
247:genetic diseases
192:Roslin Institute
5564:
5563:
5559:
5558:
5557:
5555:
5554:
5553:
5539:
5538:
5530:
5528:
5520:
5512:
5510:
5507:The Independent
5491:
5489:
5481:
5465:
5433:
5431:Further reading
5425:
5424:
5414:
5412:
5403:
5402:
5398:
5388:
5386:
5376:
5372:
5362:
5360:
5350:
5346:
5301:
5297:
5287:
5285:
5278:
5271:
5261:
5259:
5253:
5249:
5239:
5237:
5234:
5228:
5224:
5215:
5213:
5204:
5203:
5199:
5190:
5188:
5170:
5166:
5156:
5154:
5146:
5145:
5141:
5131:
5129:
5121:
5120:
5116:
5106:
5104:
5100:
5093:
5089:
5088:
5077:
5067:
5065:
5055:
5048:
5038:
5036:
5029:
5025:
5015:
5013:
5008:
5007:
5003:
4993:
4991:
4981:
4977:
4967:
4965:
4958:
4954:
4903:
4899:
4854:
4847:
4802:
4798:
4753:
4749:
4739:
4737:
4725:
4721:
4711:
4709:
4697:
4693:
4678:
4674:
4665:
4663:
4645:
4641:
4596:
4592:
4582:
4580:
4565:
4564:
4560:
4550:
4548:
4536:
4532:
4493:
4489:
4458:
4454:
4445:
4443:
4425:
4421:
4376:
4367:
4320:
4316:
4277:
4268:
4227:(26): 11657–8.
4213:
4206:
4169:
4165:
4128:
4124:
4114:
4112:
4105:
4101:
4072:
4068:
4015:
4011:
3964:
3957:
3916:(26): 12034–9.
3902:
3898:
3843:
3839:
3800:(7245): 442–5.
3786:
3777:
3740:
3736:
3699:
3695:
3655:
3651:
3641:
3639:
3601:
3597:
3544:
3540:
3501:
3494:
3465:(10): 2301–16.
3455:
3444:
3421:10.1038/nrg3686
3405:
3401:
3362:
3351:
3298:
3294:
3241:
3237:
3195:(7603): 420–4.
3181:
3174:
3137:
3133:
3078:
3074:
3064:
3062:
3047:
3043:
2988:
2984:
2939:
2935:
2890:
2886:
2857:
2853:
2830:10.1038/nrg2842
2814:
2803:
2748:
2744:
2715:(12): 1427–32.
2709:Nature Medicine
2705:
2701:
2662:
2655:
2608:
2604:
2559:
2555:
2547:
2545:
2538:
2537:
2533:
2501:
2497:
2460:
2456:
2411:
2407:
2362:
2353:
2308:
2301:
2262:
2258:
2221:
2217:
2207:
2205:
2200:
2199:
2192:
2155:
2148:
2141:
2119:
2115:
2106:
2104:
2101:Broad Institute
2095:
2094:
2090:
2035:(6563): 57–65.
2020:
2016:
2007:
2005:
1996:
1995:
1991:
1982:
1980:
1970:
1961:
1932:(7): e1900032.
1922:
1918:
1908:
1906:
1872:
1868:
1858:
1856:
1845:
1841:
1831:
1829:
1825:
1819:
1804:
1781:(6–8): 629–37.
1767:
1763:
1738:
1716:
1712:
1667:
1663:
1652:
1648:
1613:
1612:
1608:
1565:
1556:
1505:
1501:
1470:
1466:
1461:
1418:
1410:Jennifer Doudna
1404:was awarded to
1391:
1340:
1300:designer babies
1284:
1278:
1231:
1207:Dolly the sheep
1156:
1144:Hunter syndrome
1115:, and to evade
1097:
1092:
1083:
806:
774:
702:
671:electroporation
654:
629:
620:
611:
591:
585:
546:
470:
419:
413:/Cas9) system.
390:
350:
345:
328:Cre recombinase
312:
300:Oliver Smithies
288:gene expression
286:genes or alter
276:transgenic mice
260:
255:
223:
89:
38:, is a type of
17:
12:
11:
5:
5562:
5552:
5551:
5549:Genome editing
5537:
5536:
5526:yourgenome.org
5518:
5497:
5479:
5463:
5445:(4): 752–772.
5432:
5429:
5423:
5422:
5396:
5370:
5344:
5295:
5269:
5247:
5222:
5197:
5164:
5139:
5114:
5075:
5046:
5023:
5001:
4975:
4952:
4897:
4845:
4796:
4747:
4719:
4691:
4672:
4639:
4590:
4558:
4530:
4487:
4452:
4419:
4390:(22): 1463–8.
4365:
4314:
4287:(7): 1417–27.
4266:
4204:
4163:
4122:
4099:
4066:
4009:
3955:
3896:
3837:
3775:
3754:(1–2): 27–31.
3734:
3693:
3666:(4): 465–480.
3649:
3595:
3538:
3505:Nature Methods
3492:
3442:
3399:
3372:(9): 933–941.
3349:
3292:
3235:
3172:
3131:
3072:
3041:
2982:
2953:(7): 397–405.
2933:
2884:
2851:
2801:
2762:(3): 1156–60.
2742:
2699:
2666:Nature Methods
2653:
2602:
2573:(16): 5601–8.
2553:
2531:
2495:
2474:(4): 895–905.
2468:Molecular Cell
2454:
2425:(17): 3870–9.
2405:
2351:
2316:Nature Methods
2299:
2256:
2215:
2190:
2146:
2139:
2113:
2088:
2014:
1989:
1978:Science | AAAS
1959:
1916:
1866:
1839:
1802:
1761:
1736:
1710:
1661:
1646:
1619:Nature Methods
1606:
1554:
1519:(8): 600–611.
1499:
1480:(4): 752–772.
1463:
1462:
1460:
1457:
1456:
1455:
1449:
1444:
1439:
1434:
1429:
1424:
1417:
1414:
1390:
1387:
1339:
1336:
1308:sense of smell
1288:transhumanists
1280:Main article:
1277:
1274:
1230:
1227:
1155:
1152:
1096:
1093:
1091:
1088:
1085:
1084:
1082:
1081:
1074:
1067:
1059:
1056:
1055:
1054:
1053:
1048:
1043:
1035:
1034:
1030:
1029:
1028:
1027:
1022:
1017:
1012:
1007:
999:
998:
992:
991:
990:
989:
984:
977:
972:
964:
963:
957:
956:
955:
954:
949:
944:
936:
935:
933:Genome editing
929:
928:
927:
926:
921:
916:
908:
907:
901:
900:
894:
893:
805:
802:
773:
770:
769:
768:
765:
759:
754:
748:
742:
739:
701:
698:
653:
650:
628:
625:
619:
616:
610:
607:
587:Main article:
584:
581:
545:
542:
500:FokI nucleases
469:
466:
418:
415:
389:
386:
349:
346:
344:
341:
311:
308:
292:Mario Capecchi
264:gene targeting
259:
256:
254:
253:Gene targeting
251:
238:specific sites
222:
219:
211:European Union
95:Nature Methods
88:
85:
28:Genome editing
15:
9:
6:
4:
3:
2:
5561:
5550:
5547:
5546:
5544:
5527:
5523:
5519:
5509:
5508:
5503:
5498:
5488:
5484:
5480:
5476:
5472:
5468:
5464:
5460:
5456:
5452:
5448:
5444:
5440:
5435:
5434:
5428:
5410:
5406:
5400:
5385:
5381:
5374:
5359:
5355:
5348:
5340:
5336:
5331:
5326:
5322:
5318:
5314:
5310:
5306:
5299:
5283:
5276:
5274:
5258:
5251:
5233:
5226:
5211:
5210:New York Post
5207:
5201:
5187:
5183:
5179:
5175:
5168:
5153:
5149:
5143:
5128:
5124:
5118:
5099:
5092:
5086:
5084:
5082:
5080:
5064:
5060:
5053:
5051:
5034:
5027:
5011:
5005:
4990:
4986:
4983:Jorgensen E.
4979:
4963:
4956:
4948:
4944:
4940:
4936:
4932:
4928:
4924:
4920:
4917:(2): 97–101.
4916:
4912:
4908:
4901:
4893:
4889:
4884:
4879:
4875:
4871:
4867:
4863:
4859:
4852:
4850:
4841:
4837:
4832:
4827:
4823:
4819:
4816:(3): 136–43.
4815:
4811:
4807:
4800:
4792:
4788:
4783:
4778:
4774:
4770:
4766:
4762:
4758:
4751:
4736:
4735:
4730:
4723:
4708:
4707:
4702:
4695:
4687:
4683:
4676:
4662:
4658:
4654:
4653:The Telegraph
4650:
4643:
4635:
4631:
4626:
4621:
4617:
4613:
4609:
4605:
4601:
4594:
4578:
4574:
4573:
4568:
4562:
4547:
4546:
4541:
4534:
4526:
4522:
4518:
4514:
4510:
4506:
4502:
4498:
4491:
4483:
4479:
4475:
4471:
4468:(6262): 731.
4467:
4463:
4456:
4442:
4438:
4434:
4430:
4423:
4415:
4411:
4406:
4401:
4397:
4393:
4389:
4385:
4381:
4374:
4372:
4370:
4361:
4357:
4352:
4347:
4342:
4337:
4333:
4329:
4325:
4318:
4310:
4306:
4302:
4298:
4294:
4290:
4286:
4282:
4275:
4273:
4271:
4262:
4258:
4253:
4248:
4243:
4238:
4234:
4230:
4226:
4222:
4218:
4211:
4209:
4200:
4196:
4191:
4186:
4183:(1): 169–76.
4182:
4178:
4174:
4167:
4159:
4155:
4150:
4145:
4142:(7): 934–40.
4141:
4137:
4133:
4126:
4110:
4103:
4094:
4089:
4085:
4081:
4077:
4070:
4062:
4058:
4053:
4048:
4044:
4040:
4036:
4032:
4028:
4026:
4022:
4013:
4005:
4001:
3997:
3993:
3989:
3985:
3981:
3977:
3973:
3969:
3962:
3960:
3951:
3947:
3942:
3937:
3932:
3927:
3923:
3919:
3915:
3911:
3907:
3900:
3892:
3888:
3883:
3878:
3873:
3868:
3864:
3860:
3856:
3852:
3848:
3841:
3833:
3829:
3824:
3819:
3815:
3811:
3807:
3803:
3799:
3795:
3791:
3784:
3782:
3780:
3771:
3767:
3762:
3757:
3753:
3749:
3745:
3738:
3730:
3726:
3721:
3716:
3712:
3708:
3704:
3697:
3689:
3685:
3681:
3677:
3673:
3669:
3665:
3661:
3653:
3638:
3634:
3630:
3626:
3622:
3618:
3614:
3610:
3606:
3599:
3591:
3587:
3582:
3577:
3573:
3569:
3565:
3561:
3557:
3553:
3549:
3542:
3534:
3530:
3526:
3522:
3518:
3514:
3510:
3506:
3499:
3497:
3488:
3484:
3480:
3476:
3472:
3468:
3464:
3460:
3453:
3451:
3449:
3447:
3438:
3434:
3430:
3426:
3422:
3418:
3415:(5): 321–34.
3414:
3410:
3403:
3395:
3391:
3387:
3383:
3379:
3375:
3371:
3367:
3360:
3358:
3356:
3354:
3345:
3341:
3336:
3331:
3327:
3323:
3319:
3315:
3311:
3307:
3303:
3296:
3288:
3284:
3280:
3276:
3272:
3268:
3263:
3258:
3254:
3250:
3246:
3239:
3233:
3228:
3224:
3219:
3214:
3210:
3206:
3202:
3198:
3194:
3190:
3186:
3179:
3177:
3168:
3164:
3159:
3154:
3150:
3146:
3142:
3135:
3127:
3123:
3118:
3113:
3108:
3103:
3099:
3095:
3091:
3087:
3083:
3076:
3060:
3056:
3052:
3045:
3037:
3033:
3028:
3023:
3018:
3013:
3009:
3005:
3002:(7): e68464.
3001:
2997:
2993:
2986:
2978:
2974:
2969:
2964:
2960:
2956:
2952:
2948:
2944:
2937:
2929:
2925:
2920:
2915:
2911:
2907:
2904:(8): 839–47.
2903:
2899:
2895:
2888:
2879:
2874:
2870:
2866:
2862:
2855:
2847:
2843:
2839:
2835:
2831:
2827:
2824:(9): 636–46.
2823:
2819:
2812:
2810:
2808:
2806:
2797:
2793:
2788:
2783:
2778:
2773:
2769:
2765:
2761:
2757:
2753:
2746:
2738:
2734:
2730:
2726:
2722:
2718:
2714:
2710:
2703:
2695:
2691:
2687:
2683:
2679:
2675:
2671:
2667:
2660:
2658:
2649:
2645:
2641:
2637:
2633:
2629:
2625:
2621:
2617:
2613:
2606:
2598:
2594:
2589:
2584:
2580:
2576:
2572:
2568:
2564:
2557:
2543:
2542:
2535:
2527:
2523:
2519:
2515:
2512:(3): 443–58.
2511:
2507:
2499:
2491:
2487:
2482:
2477:
2473:
2469:
2465:
2458:
2450:
2446:
2441:
2436:
2432:
2428:
2424:
2420:
2416:
2409:
2401:
2397:
2392:
2387:
2383:
2379:
2375:
2371:
2367:
2360:
2358:
2356:
2347:
2343:
2339:
2335:
2330:
2325:
2321:
2317:
2313:
2306:
2304:
2295:
2291:
2287:
2283:
2279:
2275:
2271:
2267:
2260:
2252:
2248:
2243:
2238:
2234:
2230:
2226:
2219:
2203:
2197:
2195:
2186:
2182:
2177:
2172:
2168:
2164:
2160:
2153:
2151:
2142:
2136:
2131:
2130:
2124:
2117:
2102:
2098:
2092:
2084:
2080:
2076:
2072:
2067:
2062:
2058:
2054:
2050:
2046:
2042:
2038:
2034:
2030:
2026:
2018:
2003:
1999:
1993:
1979:
1975:
1968:
1966:
1964:
1955:
1951:
1947:
1943:
1939:
1935:
1931:
1927:
1920:
1905:
1901:
1897:
1893:
1889:
1885:
1881:
1877:
1870:
1854:
1850:
1843:
1824:
1817:
1815:
1813:
1811:
1809:
1807:
1798:
1794:
1789:
1784:
1780:
1776:
1772:
1765:
1757:
1753:
1748:
1743:
1739:
1737:9780124047426
1733:
1729:
1725:
1721:
1714:
1706:
1702:
1697:
1692:
1688:
1684:
1680:
1676:
1672:
1665:
1657:
1650:
1642:
1638:
1633:
1628:
1624:
1620:
1616:
1610:
1602:
1598:
1594:
1590:
1586:
1582:
1578:
1574:
1570:
1563:
1561:
1559:
1550:
1546:
1542:
1538:
1534:
1530:
1526:
1522:
1518:
1514:
1510:
1503:
1495:
1491:
1487:
1483:
1479:
1475:
1468:
1464:
1453:
1450:
1448:
1445:
1443:
1440:
1438:
1437:Prime editing
1435:
1433:
1430:
1428:
1425:
1423:
1420:
1419:
1413:
1411:
1407:
1403:
1400:In 2020, the
1398:
1396:
1393:In 2007, the
1386:
1384:
1380:
1379:bioterrorists
1377:by potential
1376:
1372:
1368:
1364:
1360:
1355:
1353:
1349:
1345:
1335:
1332:
1328:
1325:The American
1323:
1321:
1317:
1313:
1312:George Church
1309:
1305:
1301:
1297:
1293:
1289:
1283:
1273:
1271:
1267:
1262:
1258:
1254:
1250:
1247:
1243:
1240:
1235:
1226:
1224:
1223:Lulu and Nana
1220:
1216:
1212:
1208:
1204:
1200:
1195:
1193:
1189:
1188:Lulu and Nana
1185:
1181:
1177:
1171:
1167:
1165:
1161:
1151:
1149:
1145:
1141:
1137:
1133:
1129:
1124:
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1118:
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1110:
1105:
1102:
1080:
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1073:
1068:
1066:
1061:
1060:
1058:
1057:
1052:
1049:
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1042:
1039:
1038:
1037:
1036:
1032:
1031:
1026:
1023:
1021:
1018:
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1013:
1011:
1008:
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1003:
1002:
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1000:
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994:
993:
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983:
982:
978:
976:
973:
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967:
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965:
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959:
958:
953:
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939:
938:
937:
934:
931:
930:
925:
922:
920:
917:
915:
912:
911:
910:
909:
906:
903:
902:
899:
896:
895:
891:
887:
886:
883:
881:
880:Agrobacterium
877:
873:
869:
865:
864:Agrobacterium
860:
858:
852:
848:
846:
844:
839:
835:
831:
827:
823:
819:
810:
801:
797:
794:
790:
786:
784:
779:
766:
764:gene labeling
763:
760:
758:
755:
753:
749:
747:
743:
740:
737:
736:
735:
732:
729:
724:
720:
716:
706:
697:
694:
690:
682:
681:
674:
672:
666:
658:
649:
646:
641:
637:
633:
624:
615:
606:
604:
599:
595:
590:
580:
578:
573:
571:
566:
562:
561:TAL effectors
558:
550:
541:
539:
535:
531:
527:
523:
519:
517:
511:
509:
503:
501:
496:
491:
487:
485:
481:
478:
474:
465:
463:
458:
456:
450:
447:
443:
437:
435:
431:
427:
423:
422:Meganucleases
417:Meganucleases
414:
412:
408:
404:
394:
385:
382:
378:
374:
370:
366:
358:
354:
340:
338:
334:
329:
325:
321:
317:
307:
305:
301:
297:
293:
289:
285:
281:
277:
273:
269:
265:
250:
248:
244:
239:
235:
231:
227:
218:
216:
212:
208:
203:
199:
197:
193:
190:
185:
183:
179:
175:
171:
167:
163:
158:
156:
152:
148:
144:
140:
136:
133:
128:
126:
122:
118:
114:
110:
109:meganucleases
105:
103:
102:
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96:
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82:
78:
74:
70:
66:
62:
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53:
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21:
5529:. Retrieved
5525:
5511:. Retrieved
5505:
5490:. Retrieved
5486:
5474:
5470:
5442:
5438:
5426:
5413:. Retrieved
5399:
5387:. Retrieved
5384:The Guardian
5383:
5373:
5361:. Retrieved
5357:
5347:
5315:(1): 18–24.
5312:
5309:EMBO Reports
5308:
5298:
5286:. Retrieved
5280:Regalado A.
5260:. Retrieved
5250:
5238:. Retrieved
5225:
5214:. Retrieved
5209:
5200:
5189:. Retrieved
5177:
5167:
5155:. Retrieved
5151:
5142:
5130:. Retrieved
5126:
5117:
5105:. Retrieved
5098:the original
5066:. Retrieved
5063:The Guardian
5062:
5037:. Retrieved
5031:Regalado A.
5026:
5014:. Retrieved
5004:
4992:. Retrieved
4988:
4978:
4966:. Retrieved
4955:
4914:
4910:
4900:
4865:
4861:
4813:
4809:
4799:
4764:
4760:
4750:
4738:. Retrieved
4732:
4722:
4710:. Retrieved
4704:
4694:
4685:
4675:
4664:. Retrieved
4652:
4642:
4610:(1): 78–83.
4607:
4603:
4593:
4581:. Retrieved
4570:
4561:
4549:. Retrieved
4543:
4533:
4500:
4496:
4490:
4465:
4461:
4455:
4444:. Retrieved
4432:
4422:
4387:
4384:Gene Therapy
4383:
4331:
4327:
4317:
4284:
4280:
4224:
4220:
4180:
4176:
4166:
4139:
4135:
4125:
4113:. Retrieved
4102:
4083:
4079:
4069:
4034:
4030:
4024:
4020:
4012:
3971:
3967:
3913:
3909:
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3797:
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3751:
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3737:
3710:
3706:
3696:
3663:
3659:
3652:
3640:. Retrieved
3612:
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3249:Trends Genet
3248:
3238:
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3075:
3063:. Retrieved
3059:the original
3054:
3044:
2999:
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2936:
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2546:, retrieved
2544:, 2006-10-18
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2235:(6): 224–8.
2232:
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2208:December 15,
2206:. Retrieved
2166:
2162:
2128:
2116:
2105:. Retrieved
2103:. 2021-09-09
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2091:
2032:
2028:
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2006:. Retrieved
2002:ScienceAlert
2001:
1992:
1981:. Retrieved
1977:
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1907:. Retrieved
1879:
1869:
1857:. Retrieved
1852:
1842:
1832:November 30,
1830:. Retrieved
1778:
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1343:
1342:In the 2016
1341:
1324:
1304:night vision
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1239:Dana Carroll
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1232:
1196:
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1157:
1125:
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1106:
1101:gene therapy
1098:
1095:Gene therapy
1033:Other topics
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534:immune cells
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426:endonuclease
420:
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5363:27 December
5288:26 December
5262:26 December
5240:26 December
5107:27 December
5068:26 December
5039:26 December
5016:26 December
4994:26 December
4968:26 December
4706:EurekAlert!
4503:: 323–327.
3558:(1): 7753.
2672:(1): 23–6.
1859:10 February
1427:RNA editing
1422:CRISPR/Cpf1
1389:Nobel prize
1160:gene drives
1113:Alemtuzumab
1025:Mirror life
996:Xenobiology
876:Ti plasmids
838:CRISPR/Cas9
477:Zinc finger
442:mutagenesis
371:(NHEJ) and
280:knocked out
215:transposons
157:('edits').
5531:2018-04-13
5513:2016-02-11
5492:2019-02-21
5216:2017-02-17
5191:2017-02-17
4740:24 January
4712:24 January
4666:2018-08-12
4583:7 February
4551:7 February
4446:2015-11-30
3151:(4): 296.
3065:2 November
2548:2018-08-11
2107:2021-10-04
2008:2020-02-09
1983:2021-05-27
1855:. NIHvcast
1681:(1): 641.
1459:References
1363:biohackers
1266:Gene drive
1219:He Jiankui
1176:He Jiankui
1164:A. gambiae
1099:The ideal
762:Endogenous
752:stem cells
530:stem cells
381:homologous
221:Background
166:He Jiankui
149:(NHEJ) or
132:engineered
5471:Bioethics
5459:233713026
5415:7 October
5186:0362-4331
4939:1469-1795
4661:0307-1235
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3326:2162-2531
3287:236934922
3271:0168-9525
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2846:205484701
2322:(1): 27.
2083:238237947
2057:0036-8075
1954:155086967
1926:BioEssays
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1316:for sleep
1192:mosaicism
987:Protocell
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715:zebrafish
326:systems.
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155:mutations
135:nucleases
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4360:28696921
4301:27114166
4261:20554917
4199:25846201
4158:24851712
4115:16 April
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3891:20508152
3832:19404258
3770:21047873
3729:29729430
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3680:16906447
3642:29 April
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3167:28303022
3036:23869221
2996:PLOS ONE
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2928:20601939
2838:20717154
2737:23318821
2729:12415262
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2640:18987743
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2449:12202772
2400:17130168
2346:26924628
2338:22312638
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2185:26397828
2075:34591643
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1896:32424191
1797:24166445
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1541:29908711
1416:See also
1383:smallpox
1371:mousepox
1320:learning
1090:Research
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826:Zea mays
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685:1-deoxy-
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430:proteins
320:Cre-LoxP
284:knock in
145:through
143:repaired
115:(ZFNs),
83:(NHEJ).
5477:. 2020.
5330:2816623
5157:25 July
5132:25 July
4919:Bibcode
4883:4343198
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4782:7264426
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4625:4913862
4545:AP News
4462:Science
4405:2747807
4351:5592921
4309:8035222
4252:2900667
4229:Bibcode
4052:6355771
4004:4323298
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3918:Bibcode
3882:2900673
3859:Bibcode
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3802:Bibcode
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3335:6454098
3218:4873371
3197:Bibcode
3126:7545300
3094:Bibcode
3027:3711819
3004:Bibcode
2968:3694601
2919:3080757
2796:8577732
2764:Bibcode
2648:4300643
2620:Bibcode
2588:2938204
2391:1702487
2251:8928227
2066:8929163
2037:Bibcode
2029:Science
1853:YouTube
1747:3683964
1696:3564264
1601:9210810
1593:9555723
1041:Hazards
723:tobacco
594:CRISPRs
343:Process
324:Flp-FRT
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168:of the
101:Science
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5457:
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5101:(PDF)
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4521:S2CID
4305:S2CID
4000:S2CID
3684:S2CID
3633:S2CID
3529:S2CID
3483:S2CID
3433:S2CID
3390:S2CID
3283:S2CID
3117:41144
2842:S2CID
2787:40048
2733:S2CID
2690:S2CID
2644:S2CID
2342:S2CID
2290:S2CID
2079:S2CID
1950:S2CID
1900:S2CID
1826:(PDF)
1597:S2CID
1545:S2CID
1490:S2CID
1452:NgAgo
1338:Risks
1286:Many
868:T-DNA
828:. In
719:maize
618:ARCUT
544:TALEN
407:TALEN
172:(see
162:China
34:, or
30:, or
5417:2020
5391:2016
5365:2016
5335:PMID
5290:2016
5264:2016
5242:2016
5182:ISSN
5159:2021
5134:2021
5109:2016
5070:2016
5041:2016
5018:2016
4996:2016
4970:2016
4935:ISSN
4888:PMID
4862:Cell
4836:PMID
4787:PMID
4742:2019
4714:2019
4686:STAT
4657:ISSN
4630:PMID
4585:2019
4553:2019
4513:PMID
4478:PMID
4437:ISSN
4410:PMID
4356:PMID
4297:PMID
4257:PMID
4195:PMID
4154:PMID
4117:2018
4057:PMID
4025:Musa
3992:PMID
3946:PMID
3887:PMID
3828:PMID
3766:PMID
3725:PMID
3676:PMID
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3586:PMID
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3382:PMID
3340:PMID
3322:ISSN
3275:PMID
3267:ISSN
3223:PMID
3163:PMID
3122:PMID
3067:2017
3032:PMID
2973:PMID
2924:PMID
2834:PMID
2792:PMID
2725:PMID
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2636:PMID
2593:PMID
2522:PMID
2486:PMID
2445:PMID
2396:PMID
2334:PMID
2282:PMID
2247:PMID
2210:2008
2181:PMID
2135:ISBN
2071:PMID
2053:ISSN
1942:PMID
1911:2019
1892:PMID
1861:2017
1834:2015
1793:PMID
1752:PMID
1732:ISBN
1701:PMID
1637:PMID
1589:PMID
1537:PMID
1529:ISSN
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1329:and
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298:and
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125:Cas9
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5317:doi
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4777:PMC
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4620:PMC
4612:doi
4505:doi
4470:doi
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4289:doi
4247:PMC
4237:doi
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