876:
mutation in the transthyretin (TTR) gene which is inherited. Changing just one amino-acid changes the tetrameric transthyretin proteins, resulting in unstable tetrameric transthyretin protein that aggregates in monomers and forms insoluble extracellular amyloid deposits. Amyloid buildup in various organ systems causes cardiomyopathy, polyneuropathy, gastrointestinal dysfunction. It affects 50,000 people worldwide. To deliver the drug directly to the liver, siRNA is encased in a lipid nanoparticle. The siRNA molecule halts the production of amyloid proteins by interfering with the RNA production of abnormal TTR proteins. This prevents the accumulation of these proteins in different organs of the body and helps the patients manage this disease.
810:. The latter is the most efficient virus that stably delivers siRNA to target cells as it can transduce nondividing cells as well as directly target the nucleus. These specific viral vectors have been synthesized to effectively facilitate siRNA that is not viable for transfection into cells. Another aspect is that in some cases synthetic viral vectors can integrate siRNA into the cell genome which allows for stable expression of siRNA and long-term gene knockdown. This technique is advantageous because it is in vivo and effective for difficult to transfect cell. However problems arise because it can trigger antiviral responses in some cell types leading to mutagenic and immunogenic effects.
533:
for the treatment of autosomal dominant genetic disorders especially in cases where wild-type allele expression is crucial for organism survival such as
Huntington disease (HD),DYT1 dystonia (Gonzalez-Alegre et al. 2003, 2005), Alzheimer's disease (Sierant et al. 2011), Parkinson's disease (PD) (Takahashi et al. 2015), amyloid lateral sclerosis (ALS) (Schwarz et al. 2006), and Machado–Joseph disease (Alves et al. 2008). Their therapeutic potential has also been assessed for various skin disorders like epidermolysis bullosa simplex (Atkinson et al. 2011), epidermolytic palmoplantar keratoderma (EPPK) (Lyu et al. 2016), and lattice corneal dystrophy type I (LCDI) (Courtney et al. 2014).
422:(RISC). The complex silences certain gene expression by cleaving the mRNA molecules coding the target genes. To begin the process, one of the two siRNA strands, the guide strand (anti-sense strand), will be loaded into the RISC while the other strand, the passenger strand (sense strand), is degraded. Certain Dicer enzymes may be responsible for loading the guide strand into RISC. Then, the siRNA scans for and directs RISC to perfectly complementary sequence on the mRNA molecules. The cleavage of the mRNA molecules is thought to be catalyzed by the Piwi domain of
590:
transfection experiments support a model where exogenous siRNAs can saturate the endogenous RNAi machinery, resulting in the de-repression of endogenous miRNA-regulated genes. Thus, while siRNAs can produce unwanted off-target effects, i.e. unintended downregulation of mRNAs via a partial sequence match between the siRNA and target, the saturation of RNAi machinery is another distinct nonspecific effect, which involves the de-repression of miRNA-regulated genes and results in similar problems in data interpretation and potential toxicity.
559:
cytokines via toll-like receptor 7 (TLR7) has also been described. Chemical modification of siRNA is employed to reduce in the activation of the innate immune response for gene function and therapeutic applications. One promising method of reducing the nonspecific effects is to convert the siRNA into a microRNA. MicroRNAs occur naturally, and by harnessing this endogenous pathway it should be possible to achieve similar gene knockdown at comparatively low concentrations of resulting siRNAs. This should minimize nonspecific effects.
568:
partly addressed by designing appropriate control experiments, and siRNA design algorithms are currently being developed to produce siRNAs free from off-targeting. Genome-wide expression analysis, e.g., by microarray technology, can then be used to verify this and further refine the algorithms. A 2006 paper from the laboratory of Dr. Khvorova implicates 6- or 7-basepair-long stretches from position 2 onward in the siRNA matching with 3'UTR regions in off-targeted genes. The tool of siRNA off-target predition is available at
790:
transitions because of heating. This results in the making of hydrophilic pores and localized perturbations in the lipid bilayer cell membrane also causing a temporary loss of semipermeability. This allows for the escape of many intracellular contents, such as ions and metabolites as well as the simultaneous uptake of drugs, molecular probes, and nucleic acids. For cells that are difficult to transfect electroporation is advantageous however cell death is more probable under this technique.
880:
temporary relief. Before
Onpattro was released, the treatment options for hATTR were limited. After the approval of Onpattro, FDA awarded Alnylam with the Breakthrough Therapy Designation, which is given to drugs that are intended to treat a serious condition and are a substantial improvement over any available therapy. It was also awarded Orphan Drug Designations given to those treatments that are intended to safely treat conditions affecting less than 200,000 people.
4733:
463:
110:
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750:(RNAi) to be used therapeutically to reversibly silence any gene. For RNAi to realize its therapeutic potential, small interfering RNA (siRNA) must be delivered to the site of action in the cells of target tissues. But finding safe and efficient delivery mechanisms is a major obstacle to achieving the full potential of siRNA-based therapies. Unmodified siRNA is unstable in the bloodstream, has the potential to cause
333:
581:
to the oligonucleotide reducing excretion and improving circulating half-life. However recently a large Phase III trial of PEGylated RNA aptamer against factor IX had to be discontinued by Regado
Biosciences because of a severe anaphylactic reaction to the PEG part of the RNA. This reaction led to death in some cases and raises significant concerns about siRNA delivery when PEGylated oligonucleotides are involved.
273:
1139:
28:
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through which the therapies would enter the body. And that the immune system often mistakes the RNAi therapies as remnants of infectious agents, which can trigger an immune response. Animal models did not accurately represent the degree of immune response that was seen in humans and despite the promise in the treatment investors divested away from RNAi.
936:, have been submitted for new drug application to the FDA. Several siRNAs are undergoing phase 3 clinical studies, and more candidates are in the early developmental stage. In 2020, Alnylam and Vir pharmaceuticals announced a partnership and have started working on a RNAi therapy that would treat severe cases of COVID-19.
580:
Plain RNAs may be poor immunogens, but antibodies can easily be created against RNA-protein complexes. Many autoimmune diseases see these types of antibodies. There haven't yet been reports of antibodies against siRNA bound to proteins. Some methods for siRNA delivery adjoin polyethylene glycol (PEG)
532:
ASP-RNAi is an innovative category of RNAi with the objective of suppressing the dominant mutant allele while sparing expression of the corresponding normal allele with the specificity of single-nucleotide differences between the two. ASP-siRNAs are potentially a novel and better remedial alternative
875:
in adults. hATTR is a rare, progressively debilitating condition. During hATTR amyloidosis, misfolded transthyretin (TTR) protein is deposited in the extracellular space. Under typical folding conditions, TTR tetramers are made up of four monomers. Hereditary ATTR amyloidosis is caused by a fault or
846:
and
Dicerna Pharmaceuticals are few of the companies still working on bringing RNAi therapies to market. It was learned that almost all siRNA therapies administered in the bloodstream accumulated in the liver. That is why most of the early drug targets were diseases that affected the liver. Repeated
834:
basepairing with mRNA. Therefore, any target molecule that needs to be treated with high affinity and specificity can be selected if the right nucleotide sequence is available. One of the biggest challenges researchers needed to overcome was the identification and establishment of a delivery system
605:
siRNAs have been chemically modified to enhance their therapeutic properties, Short interfering RNA (siRNA) must be delivered to the site of action in the cells of target tissues in order for RNAi to fulfill its therapeutic promise. A detailed database of all such chemical modifications is manually
567:
Off-targeting is another challenge to the use of siRNAs as a gene knockdown tool. Here, genes with incomplete complementarity are inadvertently downregulated by the siRNA (in effect, the siRNA acts as a miRNA), leading to problems in data interpretation and potential toxicity. This, however, can be
789:
Electrical pulses are also used to intracellularly deliver siRNA into cells. The cell membrane is made of phospholipids which makes it susceptible to an electric field. When quick but powerful electrical pulses are initiated the lipid molecules reorient themselves, while undergoing thermal phase
731:
Currently, SiRNA are currently chemically synthesized and so, are legally categorized inside EU and in USA as simple medicinal products. But as bioengineered siRNA (BERAs) are in development, these would be classified as biological medicinal products, at least in EU. The development of the BERAs
541:
RNAi intersects with a number of other pathways; as of 2010 it was not surprising that on occasion, nonspecific effects are triggered by the experimental introduction of an siRNA. When a mammalian cell encounters a double-stranded RNA such as an siRNA, it may mistake it as a viral by-product and
680:
A huge difficulty in siRNA delivery is the problem of off-targeting. Since genes are read in both directions, there exists a possibility that even if the intended antisense siRNA strand is read and knocks out the target mRNA, the sense siRNA strand may target another protein involved in another
389:
The activity of siRNAs in RNAi is largely dependent on its binding ability to the RNA-induced silencing complex (RISC). Binding of the duplex siRNA to RISC is followed by unwinding and cleavage of the sense strand with endonucleases. The remaining anti-sense strand-RISC complex can then bind to
528:
One of the potent applications of siRNAs is the ability to distinguish the target versus non-target sequence with a single-nucleotide difference. This approach has been considered as therapeutically crucial for the silencing dominant gain-of-function (GOF) disorders,where mutant allele causing
879:
Traditionally, liver transplantation has been the standard treatment for hereditary transthyretin amyloidosis, however its effectiveness may be limited by the persistent deposition of wild-type transthyretin amyloid after transplantation. There are also small molecule medications that provide
829:
mechanism in 1993, the pharmaceutical sector heavily invested in the research and development of siRNA therapy. There are several advantages that this therapy has over small molecules and antibodies. It can be administered quarterly or every six months. Another advantage is that, unlike small
558:
Introduction of too many siRNA can result in nonspecific events due to activation of innate immune responses. Most evidence to date suggests that this is probably due to activation of the dsRNA sensor PKR, although retinoic acid-inducible gene I (RIG-I) may also be involved. The induction of
589:
siRNAs transfection into cells typically lowers the expression of many genes, however, the upregulation of genes is also observed. The upregulation of gene expression can partially be explained by the predicted gene targets of endogenous miRNAs. Computational analyses of more than 150 siRNA
475:
are responsible for the silencing of transposons and are not siRNAs. PIWI-interacting RNAs (piRNAs) are a recently-discovered class of small non-coding RNAs (ncRNAs) with a length of 21-35 nucleotides. They play a role in gene expression regulation, transposon silencing, and viral infection
801:
The gene silencing effects of transfected designed siRNA are generally transient, but this difficulty can be overcome through an RNAi approach. Delivering this siRNA from DNA templates can be done through several recombinant viral vectors based on retrovirus, adeno-associated virus,
426:
proteins of the RISC. The mRNA molecule is then cut precisely by cleaving the phosphodiester bond between the target nucleotides which are paired to siRNA residues 10 and 11, counting from the 5'end. This cleavage results in mRNA fragments that are further degraded by cellular
236:
that synthetic siRNAs could induce RNAi in mammalian cells. In 2001, the expression of a specific gene was successfully silenced by introducing chemically synthesized siRNA into mammalian cells (Tuschl et al.) These discoveries led to a surge in interest in harnessing RNAi for
454:
Sometimes cleavage of the target mRNA molecule does not occur. In some cases, the endonucleolytic cleavage of the phosphodiester backbone may be suppressed by mismatches of siRNA and target mRNA near the cleaving site. Other times, the
Argonaute proteins of the RISC lack
754:, and has difficulty readily navigating cell membranes. As a result, chemical alterations and/or delivery tools are needed to safely transfer siRNA to its site of action. There are three main techniques of delivery for siRNA that differ on efficiency and toxicity.
883:
Along with
Onpattro, another RNA interference therapeutic drug has also been discovered (Partisiran) which has property of inhibiting hepatic synthesis of transthyretin. Target messenger RNA (mRNA) is cleaved as a result by tiny interfering RNAs coupled to the
500:), have been used to study small non coding RNA-directed Transcriptional gene silencing. In human cell, RNA-directed transcriptional gene silencing was observed a decade ago when exogenous siRNAs silenced a transgenic elongation factor 1 α promoter driving a
649:
A good nanovector for siRNA delivery should protect siRNA from degradation, enrich siRNA in the target organ and facilitate the cellular uptake of siRNA. The three main groups of siRNA nanovectors are: lipid based, non-lipid organic-based, and inorganic.
253:, offering promising methods to deliver therapeutics into human subjects. However, human applications of siRNA have had significant limitations to its success. One of these being off-targeting. There is also a possibility that these therapies can trigger
260:
In recent years, siRNA therapies have been approved and new methods have been established to overcome these challenges. There are approved therapies available for commercial use and several currently in the pipeline waiting to get approval.
767:, polymer nanoparticles, and lipid conjugation. This method is advantageous because it can deliver siRNA to most types of cells, has high efficiency and reproducibility, and is offered commercially. The most common commercial reagents for
641:
and have shown only mild effectiveness in localized delivery sites, such as the human eye. Delivering pure DNA to target organisms is challenging because its large size and structure prevents it from diffusing readily across
722:
Proof of concept trials have indicated that Ebola-targeted siRNAs may be effective as post-exposure prophylaxis in humans, with 100% of non-human primates surviving a lethal dose of Zaire
Ebolavirus, the most lethal strain.
3126:
Gomes MJ, Dreier J, Brewer J, Martins S, Brandl M, Sarmento B (April 2016). "A new approach for a blood-brain barrier model based on phospholipid vesicles: Membrane development and siRNA-loaded nanoparticles permeability".
762:
In this technique siRNA first must be designed against the target gene. Once the siRNA is configured against the gene it has to be effectively delivered through a transfection protocol. Delivery is usually done by
311:
The mRNA is now cut and recognized as abnormal by the cell. This causes degradation of the mRNA and in turn no translation of the mRNA into amino acids and then proteins. Thus silencing the gene that encodes that
677:. siRNAs that target and silence efflux proteins on the BBB surface have been shown to create an increase in BBB permeability. siRNA delivered via lipid based nanoparticles is able to cross the BBB completely.
550:, the introduction of an siRNA may cause unintended off-targeting. Chemical modifications of siRNA may alter the thermodynamic properties that also result in a loss of single nucleotide specificity.
888:. Patisiran, an investigational RNAi therapeutic drug, uses this process to decrease the production of mutant and wild-type transthyretin by cleaving on 3-untranslated region of transthyretin mRNA.
732:
technology raises the question of the categorization of drugs having the same mechanism of action but being produced chemically or biologically. This lack of consistency should be addressed.
2356:
Birmingham A, Anderson EM, Reynolds A, Ilsley-Tyree D, Leake D, Fedorov Y, et al. (March 2006). "3' UTR seed matches, but not overall identity, are associated with RNAi off-targets".
402:. It has been shown that dsRNAs targeting gene promoters induce potent transcriptional activation of associated genes. RNAa was demonstrated in human cells using synthetic dsRNAs, termed "
447:). Dissociation of the target mRNA strand from RISC after the cleavage allow more mRNA to be silenced. This dissociation process is likely to be promoted by extrinsic factors driven by
529:
disease is differed from wt-allele by a single nucleotide (nt). These types of siRNAs with the capability to distinguish a single-nt difference, are termed as, allele-specific siRNAs.
909:
Years of research has led to a greater understanding of siRNA therapies beyond those affecting the liver. As of 2019, Alnylam
Pharmaceuticals was involved in therapies that may treat
257:. Animal models have not been successful in accurately representing the extent of this response in humans. Hence, studying the effects of siRNA therapies has been a challenge.
2548:
Grimm D, Streetz KL, Jopling CL, Storm TA, Pandey K, Davis CR, et al. (May 2006). "Fatality in mice due to oversaturation of cellular microRNA/short hairpin RNA pathways".
2656:
Hickerson RP, Smith FJ, Reeves RE, Contag CH, Leake D, Leachman SA, et al. (March 2008). "Single-nucleotide-specific siRNA targeting in a dominant-negative skin model".
906:(ALAS1), a liver enzyme involved in an early step in heme production. The downregulation of ALAS1 lowers the levels of neurotoxic intermediates that cause AHP symptoms.
1305:
Elbashir SM, Harborth J, Lendeckel W, Yalcin A, Weber K, Tuschl T (May 2001). "Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells".
899:(PBG) molecules which are formed during the production of heme. These molecules accumulate in different organs and this can lead to the symptoms or attacks of AHP.
793:
This method has been used to deliver siRNA targeting VEGF into the xenografted tumors in nude mice, which resulted in a significant suppression of tumor growth.
3823:
3798:
324:
and have broader specificity of action, while siRNAs typically work with higher specificity by cleaving the mRNA before translation, with 100% complementarity.
851:
molecule to reduce the immune response, subsequently causing little to no side effects. Listed below are some of approved therapies or therapies in pipeline.
351:
of exogenous siRNA is often unsatisfactory because the effect is only transient, especially in rapidly dividing cells. This may be overcome by creating an
1033:
Laganà A, Veneziano D, Russo F, Pulvirenti A, Giugno R, Croce CM, Ferro A (2015). "Computational Design of
Artificial RNA Molecules for Gene Regulation".
654:
based nanovectors are excellent for delivering siRNA to solid tumors, but other cancers may require different non-lipid based organic nanovectors such as
646:. siRNA oligos circumvent this problem due to their small size of 21-23 oligos. This allows delivery via nano-scale delivery vehicles called nanovectors.
459:
activity even when the target mRNA and siRNA are perfectly paired. In such cases, gene expression will be silenced by an miRNA induced mechanism instead
155:
by a synthetic siRNA with a complementary sequence, siRNAs are an important tool for validating gene function and drug targeting in the post-genomic era.
285:. Dicer cuts the long dsRNA to form short interfering RNA or siRNA; this is what enables the molecules to form the RNA-Induced Silencing Complex (RISC).
2401:"ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy"
1097:"ASPsiRNA: A Resource of ASP-siRNAs Having Therapeutic Potential for Human Genetic Disorders and Algorithm for Prediction of Their Inhibitory Efficacy"
3070:"Administration in non-human primates of escalating intravenous doses of targeted nanoparticles containing ribonucleotide reductase subunit M2 siRNA"
711:). The results showed clinical benefits, with the cancer either stabilized after six months, or regression of metastasis in some of the patients.
1700:
476:
inhibition. Once considered as "dark matter" of ncRNAs, piRNAs emerged as important players in multiple cellular functions in different organisms.
2067:
Jackson AL, Linsley PS (January 2010). "Recognizing and avoiding siRNA off-target effects for target identification and therapeutic application".
2313:
Barøy T, Sørensen K, Lindeberg MM, Frengen E (June 2010). "shRNA expression constructs designed directly from siRNA oligonucleotide sequences".
719:
samples from the patients revealed the presence of the RNAi constructs in the samples, proving that the molecules reached the intended target.
504:(GFP) reporter gene. The main mechanisms of transcriptional gene silencing (TGS) involving the RNAi machinery include DNA methylation, histone
466:
A simplified version of the Ping-Pong Method, involving proteins
Aubergine (Aub) and Argonaute-3 (Ago3) cleaving the 3' and 5' ends of piRNA.
250:
281:
Long dsRNA (which can come from hairpin, complementary RNAs, and RNA-dependent RNA polymerases) is cleaved by an endo-ribonuclease called
398:
It has been found that dsRNA can also activate gene expression, a mechanism that has been termed "small RNA-induced gene activation" or
3279:"Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study"
2754:"Designing potential siRNA molecules for silencing the gene of the nucleocapsid protein of Nipah virus: A computational investigation"
1964:"Computational Identification of piRNAs Using Features Based on RNA Sequence, Structure, Thermodynamic and Physicochemical Properties"
3913:
1911:
3459:"Comparison of small interfering RNA (siRNA) delivery into bovine monocyte-derived macrophages by transfection and electroporation"
2221:
Whitehead KA, Dahlman JE, Langer RS, Anderson DG (17 June 2011). "Silencing or stimulation? siRNA delivery and the immune system".
1413:
1159:, Caudy AA, Hammond SM, Hannon GJ (January 2001). "Role for a bidentate ribonuclease in the initiation step of RNA interference".
298:
The strand that is thermodynamically less stable due to its base pairing at the 5´end is chosen to remain part of the RISC-complex
4328:
610:
in scientific literature. Chemical modification of siRNA can also inadvertently result in loss of single-nucleotide specificity.
625:
One of the biggest challenges to siRNA and RNAi based therapeutics is intracellular delivery. siRNA also has weak stability and
4066:
3204:
630:
245:. Significant developments in siRNA therapies have been made with both organic (carbon based) and inorganic (non-carbon based)
1262:
Hamilton AJ, Baulcombe DC (October 1999). "A species of small antisense RNA in posttranscriptional gene silencing in plants".
3667:
3585:
3552:
1637:
1050:
513:
3328:"RNA-based drugs and regulation: Toward a necessary evolution of the definitions issued from the European union legislation"
703:. The RNAi targeted two genes encoding key proteins in the growth of the cancer cells, vascular endothelial growth factor, (
3238:"First-in-humans trial of an RNA interference therapeutic targeting VEGF and KSP in cancer patients with liver involvement"
410:
mosquito has shown there is some evidence for RNAa and can be achieved by short or long dsRNAs targeting promoter regions.
939:
Other companies that have had success in developing a pipeline of siRNA therapies are Dicerna Pharmaceuticals, partnered
696:
440:
432:
2703:"Analysis of gene expression profiles in HeLa cells in response to overexpression or siRNA-mediated depletion of NASP"
1356:
Chen, Zhihang; Krishnamachary, Balaji; Pachecho-Torres, Jesus; Penet, Marie-France; Bhujwalla, Zaver M. (March 2020).
4414:
2758:
Infection, Genetics and Evolution: Journal of Molecular Epidemiology and Evolutionary Genetics in Infectious Diseases
3650:
Cambon K, Déglon N (2013). "Lentiviral-Mediated Gene Transfer of siRNAs for the Treatment of Huntington's Disease".
2174:"Modified siRNA structure with a single nucleotide bulge overcomes conventional siRNA-mediated off-target silencing"
688:, aka AMD) reported at the end of 2005 that siRNAs are well tolerated and have suitable pharmacokinetic properties.
4701:
4172:
685:
505:
168:
90:
959:
have also invested heavily in siRNA therapies as they see the potential success of this area of biological drugs.
320:, however, miRNAs are derived from shorter stemloop RNA products. miRNAs typically silence genes by repression of
4706:
4100:
830:
molecule and monoclonal antibodies that need to recognize specific conformation of a protein, siRNA functions by
3889:"Vir and Alnylam Expand Collaboration to Advance Investigational RNAi Therapeutics Targeting Host Factors for t"
269:
The mechanism by which natural siRNA causes gene silencing through repression of translation occurs as follows:
4762:
2808:
Petrocca F, Lieberman J (February 2011). "Promise and challenge of RNA interference-based therapy for cancer".
355:
for the siRNA. The siRNA sequence is modified to introduce a short loop between the two strands. The resulting
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4489:
885:
444:
419:
289:
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Hannon GJ, Rossi JJ (September 2004). "Unlocking the potential of the human genome with RNA interference".
2405:
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903:
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and Neon Transfection. However, it is not compatible with all cell types and has low in vivo efficiency.
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promoter (e.g., U6 or H1) to direct the transcription of small nuclear RNAs (snRNAs) (U6 is involved in
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component of human RNase P). It is theorized that the resulting siRNA transcript is then processed by
301:
The single stranded siRNA which is part of the RISC complex now can scan and find a complementary mRNA
3222:
978:
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922:
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modulate gene expression largely via incomplete complementarity base pair interactions with a target
501:
2670:
895:
used to treat acute hepatic porphyria (AHP). The disease is caused due to the accumulation of toxic
838:
However, there were a few companies that continued with the development of RNAi therapy for humans.
4285:
3236:
Tabernero J, Shapiro GI, LoRusso PM, Cervantes A, Schwartz GK, Weiss GJ, et al. (April 2013).
3223:"First-in-man study demonstrates the therapeutic effect of RNAi gene silencing in cancer treatment"
813:
This method has potential use in gene silencing of the central nervous system for the treatment of
489:
356:
198:
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Mahfuz A, Khan MA, Sajib EH, Deb A, Mahmud S, Hasan M, Saha O, Islam A, Rahaman MM (August 2022).
406:" (saRNAs). It is currently not known how conserved RNAa is in other organisms. One report in the
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3205:"Promising eye drug from S.F. firm / Macular degeneration treatment interferes with RNA messages"
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siRNAs delivered via lipid based nanoparticles have been shown to have therapeutic potential for
493:
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1443:"VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and their targets"
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Once the single stranded siRNA (part of the RISC complex) binds to its target mRNA, it induces
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Once the siRNA is part of the RISC complex, the siRNA is unwound to form single stranded siRNA.
185:
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As of 2020, ONPATTRO and GIVLAARI, were available for commercial application, and two siRNAs,
871:
was approved for the treatment of polyneuropathy of hereditary transthyretin-mediated (hATTR)
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Eisenstein M (16 October 2019). "Pharma's roller-coaster relationship with RNA therapies".
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Naturally occurring siRNAs have a well-defined structure that is a short (usually 20 to 24-
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around DNA matching the siRNA, effectively silencing the genes in that region of the DNA.
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The siRNA-induced post transcriptional gene silencing is initiated by the assembly of the
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1716:"Distinct roles for Drosophila Dicer-1 and Dicer-2 in the siRNA/miRNA silencing pathways"
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Geisbert TW, Lee AC, Robbins M, Geisbert JB, Honko AN, Sood V, et al. (May 2010).
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around the target gene into a heterochromatic state. SiRNAs can be incorporated into a
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2501:"Transfection of small RNAs globally perturbs gene regulation by endogenous microRNAs"
1981:
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1655:"RNA activation in insects: The targeted activation of endogenous and exogenous genes"
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via siRNAs has generated a great deal of interest in both basic and applied biology.
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Sharei A, Zoldan J, Adamo A, Sim WY, Cho N, Jackson E, et al. (February 2013).
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3824:"FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease"
3799:"FDA approves first-of-its kind targeted RNA-based therapy to treat a rare disease"
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3712:
3704:
3655:
3622:
3614:
3540:
3478:
3470:
3405:
3357:
3339:
3298:
3290:
3249:
3175:
3167:
3136:
3091:
3081:
3040:
3032:
2991:
2987:
2983:
2937:
2929:
2879:
2871:
2817:
2765:
2724:
2714:
2675:
2628:
2620:
2565:
2520:
2512:
2471:
2463:
2422:
2414:
2400:
2365:
2322:
2285:
2277:
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2193:
2185:
2144:
2134:
2076:
2039:
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1985:
1977:
1968:
1928:
1882:
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1833:
1787:
1779:
1749:
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1666:
1585:
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1385:
1369:
1322:
1271:
1236:
1196:
1176:
1118:
1110:
1096:
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1038:
826:
747:
626:
619:
569:
242:
231:
213:
194:
180:
70:
20:
1714:
Lee YS, Nakahara K, Pham JW, Kim K, He Z, Sontheimer EJ, Carthew RW (April 2004).
1358:"Theranostic small interfering RNA nanoparticles in cancer precision nanomedicine"
1342:
359:
is a short hairpin RNA (shRNA), which can be processed into a functional siRNA by
77:
of specific genes with complementary nucleotide sequences by degrading mRNA after
4571:
4542:
4254:
3544:
3474:
3254:
3237:
3140:
2770:
1863:"Decay of mRNAs targeted by RISC requires XRN1, the Ski complex, and the exosome"
1275:
1156:
1042:
896:
784:
712:
634:
517:
436:
205:
125:
74:
3659:
3068:
Heidel JD, Yu Z, Liu JY, Rele SM, Liang Y, Zeidan RK, et al. (April 2007).
847:
developmental work also shed light on improving the chemical composition of the
288:
Once siRNA enters the cell it gets incorporated into other proteins to form the
4663:
4566:
4383:
4013:
3757:
3074:
Proceedings of the National Academy of Sciences of the United States of America
2119:
Proceedings of the National Academy of Sciences of the United States of America
1783:
1670:
1560:
Proceedings of the National Academy of Sciences of the United States of America
1240:
1143:
973:
968:
751:
448:
399:
344:
337:
327:
201:
152:
55:
3344:
2875:
2326:
1963:
1932:
1458:
4751:
4598:
4588:
4469:
4424:
4402:
4238:
4167:
4095:
4090:
3765:
3353:
2821:
2779:
2601:"siRNAmod: A database of experimentally validated chemically modified siRNAs"
1381:
772:
666:
547:
305:
227:
129:
3086:
2139:
1580:
4757:
4681:
4501:
4474:
4419:
4338:
4295:
4105:
4031:
3988:
Du Rietz H, Hedlund H, Wilhelmson S, Nordenfelt P, Wittrup A (April 2020).
3972:
3914:"Alnylam and Dicerna are pals now, which could spell trouble for Arrowhead"
3874:
3783:
3726:
3708:
3677:
3636:
3562:
3510:(8th ed.). New Delhi: Jaypee Brothers Medical Publishers. p. 304.
3492:
3417:
3371:
3312:
3263:
3189:
3105:
3054:
3005:
2951:
2893:
2829:
2787:
2753:
2738:
2719:
2687:
2679:
2642:
2577:
2534:
2485:
2436:
2377:
2334:
2299:
2242:
2207:
2088:
2053:
1999:
1940:
1896:
1847:
1801:
1741:
1678:
1654:
1599:
1511:
1476:
1399:
1334:
1283:
1188:
1132:
1070:
768:
655:
456:
372:
348:
246:
148:
3855:
3839:"Patisiran, an RNAi Therapeutic, for Hereditary Transthyretin Amyloidosis"
3838:
3618:
2418:
2158:
1114:
4593:
4439:
4306:
3742:"Recent advances in siRNA delivery mediated by lipid-based nanoparticles"
2034:
956:
910:
872:
726:
428:
383:
190:
172:
164:
94:
86:
4394:
3964:
2933:
2569:
2499:
Khan AA, Betel D, Miller ML, Sander C, Leslie CS, Marks DS (June 2009).
2189:
1878:
1838:
1821:
1628:
Li LC (2008). "Small RNA-Mediated Gene Activation". In Morris KV (ed.).
1503:
684:
Phase I results of the first two therapeutic RNAi trials (indicated for
607:
4653:
4362:
4357:
4352:
4259:
4233:
3865:
3535:
Takei Y (2014). "Electroporation-Mediated siRNA Delivery into Tumors".
3388:
Rosemary, Kanasty (2013). "Delivery materials for siRNA therapeutics".
3225:(Press release). Vall d'Hebron Institute of Oncology. 11 February 2013.
3036:
1630:
RNA and the Regulation of Gene Expression: A Hidden Layer of Complexity
998:
933:
807:
803:
692:
497:
462:
3578:
Textbook of Biochemistry, Biotechnology, Allied and Molecular Medicine
3383:
3381:
3171:
2858:
Hu B, Zhong L, Weng Y, Peng L, Huang Y, Zhao Y, Liang XJ (June 2020).
2624:
2355:
1652:
1373:
1355:
4517:
4290:
4264:
4146:
4136:
3409:
2516:
2369:
1326:
1180:
1013:
1008:
929:
892:
868:
542:
mount an immune response. Furthermore, because structurally related
516:(RITS) complex. An active RITS complex will trigger the formation of
423:
117:
62:
2700:
2467:
2080:
272:
4671:
4522:
4452:
4187:
3987:
3826:(Press release). U.S. Food and Drug Administration. 10 August 2018.
3378:
988:
643:
638:
618:
Given the ability to knock down, in essence, any gene of interest,
543:
317:
109:
66:
58:
3693:"RNAi-based therapeutics-current status, challenges and prospects"
1441:
Qureshi A, Thakur N, Monga I, Thakur A, Kumar M (1 January 2014).
1037:. Methods in Molecular Biology. Vol. 1269. pp. 393–412.
598:
4676:
4197:
4141:
3654:. Methods in Molecular Biology. Vol. 1010. pp. 95–109.
863:
became the first company to have a siRNA therapy approved by the
332:
217:
3539:. Methods in Molecular Biology. Vol. 1121. pp. 131–8.
3235:
2452:"Knocking down disease: a progress report on siRNA therapeutics"
1556:"A vector-free microfluidic platform for intracellular delivery"
183:
mechanism while working on the gene expression in the nematode,
4691:
4686:
4636:
4269:
4177:
4044:
2972:"RNA-based therapeutics: current progress and future prospects"
1613:
Daneholt, B. (2006). "Advanced Information: RNA interference".
1304:
1003:
993:
983:
902:
Givlaari is an siRNA drug that downregulates the expression of
716:
523:
136:
3603:"Lentiviral-mediated delivery of siRNAs for antiviral therapy"
3521:
2701:
Alekseev OM, Richardson RT, Alekseev O, O'Rand MG (May 2009).
2220:
1910:
Ozata DM, Gainetdinov I, Zoch A, Phillip D, Zamore PD (2019).
1032:
691:
In a phase 1 clinical trial, 41 patients with advanced cancer
4494:
4151:
2312:
1142:
Text was copied from this source, which is available under a
1138:
952:
674:
651:
376:
363:
in its usual fashion. Typical transcription cassettes use an
360:
282:
140:
133:
27:
3021:"RNA interference is mediated by 21- and 22-nucleotide RNAs"
637:
in vivo are vulnerable to degradation by plasma and tissue
382:
The gene knockdown efficiency can also be improved by using
328:
RNAi induction using siRNAs or their biosynthetic precursors
3580:(4th ed.). PHI Learning Private Limited. p. 873.
2266:"Function and regulation of retinoic acid-inducible gene-I"
1909:
1155:
704:
673:(BBB) often blocks access of potential therapeutics to the
536:
3990:"Imaging small molecule-induced endosomal escape of siRNA"
3432:
3276:
2655:
613:
4556:
4377:
4076:
848:
3125:
2547:
2399:
Monga I, Qureshi A, Thakur N, Gupta AK, Kumar M (2017).
1440:
1095:
Monga I, Qureshi A, Thakur N, Gupta AK, Kumar M (2017).
3740:
Yonezawa, Sei; Koide, Hiroyuki; Asai, Tomohiro (2020).
3018:
2398:
1490:
Mack GS (June 2007). "MicroRNA gets down to business".
1094:
390:
target mRNAs for initiating transcriptional silencing.
31:
Mediating RNA interference in cultured mammalian cells.
3156:"Peptides used in the delivery of small noncoding RNA"
2223:
Annual Review of Chemical and Biomolecular Engineering
1912:"PIWI-interacting RNAs: small RNAs with big functions"
1414:"New Kind of Drug, Silencing Genes, Gets FDA Approval"
1144:
Creative Commons Attribution 4.0 International License
925:
to develop therapies for CNS, eye and liver diseases.
727:
Legal categorization and legal issues in a near future
669:. Central nervous disorders are not uncommon, but the
413:
2599:
Dar SA, Thakur A, Qureshi A, Kumar M (January 2016).
2598:
2498:
951:. Several other big pharmaceutical companies such as
1553:
3456:
3121:
3119:
3117:
3115:
3019:Elbashir SM, Lendeckel W, Tuschl T (January 2001).
2263:
2115:"Specificity of antisense oligonucleotides in vivo"
2112:
2011:
2009:
584:
3575:
2751:
1713:
3893:Investor Relations | Alnylam Pharmaceuticals, Inc
3739:
2918:"Nanovector delivery of siRNA for cancer therapy"
2807:
2016:Marc S, Weinberg; Kevin V, Morris (August 2016).
1765:
1261:
1214:
1212:
1210:
1208:
1206:
479:
4749:
3112:
2803:
2801:
2799:
2797:
2449:
2113:Woolf TM, Melton DA, Jennings CG (August 1992).
2006:
570:http://crdd.osdd.net/servers/aspsirna/asptar.php
3576:Talwar GP, Hasnain S, Sarin SK (January 2016).
3067:
2965:
2963:
2961:
2857:
2172:Dua P, Yoo JW, Kim S, Lee DK (September 2011).
1860:
1815:
1813:
1811:
1761:
1759:
1653:De Hayr L, Asad S, Hussain M, Asgari S (2020).
891:In 2019, FDA approved the second RNAi therapy,
3457:Jensen K, Anderson JA, Glass EJ (April 2014).
3325:
3153:
2915:
2108:
2106:
2066:
1203:
1090:
1088:
1086:
1084:
1082:
1080:
147:. siRNAs can also be introduced into cells by
132:3' ends with two overhanging nucleotides. The
4322:
4060:
3797:Commissioner, Office of the (24 March 2020).
3522:"siRNA Delivery Methods into Mammalian Cells"
2794:
2392:
2015:
1961:
1768:"Origins and Mechanisms of miRNAs and siRNAs"
1434:
3796:
3690:
3649:
3594:
3270:
3147:
3061:
3012:
2969:
2958:
2911:
2909:
2907:
2905:
2903:
2592:
2214:
2171:
1955:
1903:
1819:
1808:
1756:
1699:: CS1 maint: multiple names: authors list (
1646:
1612:
1547:
575:
524:Applications: Allele-specific gene silencing
3942:
3600:
3326:Guerriaud, Mathieu; Kohli, Evelyne (2022).
2103:
1766:Carthew RW, Sontheimer EJ (February 2009).
1077:
439:while the 3' fragment is degraded from its
4336:
4329:
4315:
4067:
4053:
3505:
3154:Shukla RS, Qin B, Cheng K (October 2014).
2853:
2851:
2849:
2847:
2018:"Transcriptional gene silencing in humans"
1218:
854:
796:
4021:
3864:
3854:
3773:
3716:
3626:
3482:
3463:Veterinary Immunology and Immunopathology
3361:
3343:
3302:
3253:
3179:
3095:
3085:
3044:
2995:
2941:
2900:
2883:
2769:
2728:
2718:
2669:
2632:
2524:
2475:
2450:Wittrup A, Lieberman J (September 2015).
2426:
2289:
2197:
2148:
2138:
2043:
2033:
1989:
1886:
1837:
1791:
1731:
1615:The Novel Prize in Physiology or Medicine
1589:
1579:
1466:
1389:
1122:
1060:
735:
139:catalyzes production of siRNAs from long
3387:
2864:Signal Transduction and Targeted Therapy
2658:The Journal of Investigative Dermatology
2235:10.1146/annurev-chembioeng-061010-114133
1362:WIREs Nanomedicine and Nanobiotechnology
597:
593:
537:Challenges: avoiding nonspecific effects
461:
331:
271:
108:
73:(RNAi) pathway. It interferes with the
26:
3430:
2844:
614:Therapeutic applications and challenges
431:. The 5' fragment is degraded from its
197:in 2006. siRNAs and their role in post-
4750:
3202:
2916:Shen H, Sun T, Ferrari M (June 2012).
2707:Reproductive Biology and Endocrinology
4310:
4048:
3836:
3534:
2970:Burnett JC, Rossi JJ (January 2012).
2860:"Therapeutic siRNA: state of the art"
1861:Orban TI, Izaurralde E (April 2005).
514:RNA-induced transcriptional silencing
484:Many model organism, such as plants (
151:. Since in principle any gene can be
1621:
1489:
572:and published as ASPsiRNA resource.
3843:The New England Journal of Medicine
2264:Matsumiya T, Stafforini DM (2010).
414:Post-transcriptional gene silencing
204:(PTGS) was discovered in plants by
13:
3935:
3601:Morris KV, Rossi JJ (March 2006).
1820:Tomari Y, Zamore PD (March 2005).
1627:
778:
553:
14:
4784:
4453:Micro
4040:
3691:Tiemann K, Rossi JJ (June 2009).
1982:10.2174/1389202920666191129112705
393:
4732:
4731:
4173:Cis-natural antisense transcript
4074:
3508:Textbook of Medical Biochemistry
2282:10.1615/critrevimmunol.v30.i6.10
1822:"Perspective: machines for RNAi"
1137:
921:. They have also partnered with
825:A decade after the discovery of
707:), and kinesin spindle protein (
686:age-related macular degeneration
629:behavior. Delivery of siRNA via
585:Saturation of the RNAi machinery
562:
506:post-translational modifications
249:, which have been successful in
230:and colleagues soon reported in
169:Carnegie Institution for Science
91:Carnegie Institution for Science
85:. It was discovered in 1998, by
61:, typically 20–24 (normally 21)
4408:precursor, heterogenous nuclear
4101:Signal recognition particle RNA
3906:
3881:
3830:
3816:
3790:
3733:
3684:
3643:
3569:
3528:
3514:
3499:
3450:
3424:
3319:
3229:
3215:
3196:
2745:
2694:
2649:
2541:
2492:
2443:
2349:
2306:
2257:
2165:
2060:
1854:
1707:
1606:
1526:
1483:
757:
4538:Trans-acting small interfering
4502:Enhancer RNAs
4420:Transfer
3746:Advanced Drug Delivery Reviews
3652:Trinucleotide Repeat Protocols
2988:10.1016/j.chembiol.2011.12.008
2270:Critical Reviews in Immunology
1406:
1349:
1298:
1255:
1149:
1026:
904:aminolevulinic acid synthase 1
639:endonucleases and exonucleases
480:Transcriptional Gene Silencing
1:
4425:Ribosomal
4403:Messenger
3295:10.1016/S0140-6736(10)60357-1
2406:G3: Genes, Genomes, Genetics
2069:Nature Reviews Drug Discovery
1733:10.1016/s0092-8674(04)00261-2
1019:
886:RNA-induced silencing complex
746:There is great potential for
420:RNA-induced silencing complex
3837:David, Adams (5 July 2018).
3545:10.1007/978-1-4614-9632-8_11
3475:10.1016/j.vetimm.2014.02.002
3255:10.1158/2159-8290.CD-12-0429
3141:10.1016/j.memsci.2016.01.002
2810:Journal of Clinical Oncology
2771:10.1016/j.meegid.2022.105310
1962:Monga I, Banerjee I (2019).
1276:10.1126/science.286.5441.950
1102:G3: Genes, Genomes, Genetics
1043:10.1007/978-1-4939-2291-8_25
820:
443:by 5' -3' exoribonuclease 1(
264:
179:in Worcester discovered the
104:
7:
3660:10.1007/978-1-62703-411-1_7
3203:Tansey B (11 August 2006).
3129:Journal of Membrane Science
962:
177:University of Massachusetts
99:University of Massachusetts
69:, and operating within the
10:
4789:
4604:Multicopy single-stranded
4448:Interferential
4260:Reverse transcribing virus
4014:10.1038/s41467-020-15300-1
3758:10.1016/j.addr.2020.07.022
1784:10.1016/j.cell.2009.01.035
1671:10.1016/j.ibmb.2020.103325
1632:. Caister Academic Press.
1241:10.1038/d41586-019-03069-3
782:
739:
490:Saccharomyces cerevisiae
251:drug delivery to the brain
158:
18:
4727:
4662:
4612:
4555:
4518:Guide
4510:
4438:
4393:
4376:
4345:
4278:
4247:
4226:
4160:
4119:
4083:
3537:Electroporation Protocols
3345:10.3389/fmed.2022.1012497
2876:10.1038/s41392-020-0207-x
2327:10.1007/s12033-010-9247-8
1933:10.1038/s41576-018-0073-3
1534:"RNA Interference (RNAi)"
979:Oligonucleotide synthesis
945:Arrowhead Pharmaceuticals
923:Regeneron Pharmaceuticals
633:has shown promise. siRNA
576:Adaptive immune responses
502:Green Fluorescent Protein
336:Dicer protein colored by
316:siRNA is also similar to
4480:Small nuclear
2822:10.1200/JCO.2009.27.6287
2456:Nature Reviews. Genetics
193:for their research with
4594:Genomic
4227:Cis-regulatory elements
4198:Repeat-associated siRNA
3697:EMBO Molecular Medicine
3160:Molecular Pharmaceutics
3087:10.1073/pnas.0701458104
3025:Genes & Development
2976:Chemistry & Biology
2315:Molecular Biotechnology
2140:10.1073/pnas.89.16.7305
1920:Nature Reviews Genetics
1826:Genes & Development
1659:Insect Biochem Mol Biol
1581:10.1073/pnas.1218705110
1459:10.1093/database/bau103
1419:The Wall Street Journal
913:and CNS disorders like
861:Alnylam Pharmaceuticals
855:Alnylam Pharmaceuticals
840:Alnylam Pharmaceuticals
797:Viral-mediated delivery
494:Drosophila melanogaster
4697:Artificial chromosomes
4485:Small nucleolar
4111:Transfer-messenger RNA
3709:10.1002/emmm.200900023
3506:Chatterjea MN (2012).
2720:10.1186/1477-7827-7-45
2680:10.1038/sj.jid.5701060
2022:Nucleic Acids Research
742:Intracellular delivery
736:Intracellular delivery
663:central nervous system
602:
467:
341:
277:
186:Caenorhabditis elegans
113:
65:in length, similar to
42:), sometimes known as
32:
4763:Small interfering RNA
4490:Small Cajal Body RNAs
4203:Small interfering RNA
3994:Nature Communications
3856:10.1056/NEJMoa1716153
3619:10.1038/sj.gt.3302688
3332:Frontiers in Medicine
2419:10.1534/g3.117.044024
1115:10.1534/g3.117.044024
941:Eli Lilly and Company
658:based nanoparticles.
601:
594:Chemical modification
473:Piwi-interacting RNAs
465:
404:small activating RNAs
335:
275:
171:in Washington DC and
112:
93:in Washington DC and
44:short interfering RNA
36:Small interfering RNA
30:
4543:Subgenomic messenger
4458:Small interfering
4430:Transfer-messenger
4193:Piwi-interacting RNA
2505:Nature Biotechnology
1492:Nature Biotechnology
915:Huntington's disease
893:Givlaari (givosiran)
869:Onpattro (patisiran)
815:Huntington's disease
510:chromatin remodeling
486:Arabidopsis thaliana
210:Sainsbury Laboratory
4132:Small nucleolar RNA
4006:2020NatCo..11.1809D
3965:10.1038/nature02870
3957:2004Natur.431..371H
3402:2013NatMa..12..967K
2934:10.1038/cgt.2012.22
2922:Cancer Gene Therapy
2617:2016NatSR...620031D
2570:10.1038/nature04791
2562:2006Natur.441..537G
2190:10.1038/mt.2011.109
2131:1992PNAS...89.7305W
1879:10.1261/rna.7231505
1839:10.1101/gad.1284105
1572:2013PNAS..110.2082S
1504:10.1038/nbt0607-631
1319:2001Natur.411..494E
1233:2019Natur.574S...4E
1173:2001Natur.409..363B
949:Johnson and Johnson
919:Alzheimer's disease
701:lipid nanoparticles
671:blood brain barrier
239:biomedical research
122:double-stranded RNA
52:double-stranded RNA
4572:Chloroplast
4415:modified Messenger
4378:Ribonucleic acids
4213:Trans-acting siRNA
4208:Small temporal RNA
4183:Long noncoding RNA
3524:. 13 October 2016.
3431:Fanelli A (2016).
3289:(9729): 1896–905.
3037:10.1101/gad.862301
2605:Scientific Reports
2035:10.1093/nar/gkw139
1035:RNA Bioinformatics
844:Sirna Therapeutics
765:cationic liposomes
699:delivered through
603:
468:
365:RNA polymerase III
342:
278:
145:small hairpin RNAs
114:
33:
4768:Molecular biology
4745:
4744:
4622:Xeno
4584:Complementary
4557:Deoxyribonucleic
4551:
4550:
4528:Small hairpin
4304:
4303:
4218:Short hairpin RNA
4127:Small nuclear RNA
4084:Protein synthesis
3669:978-1-62703-410-4
3587:978-81-203-5125-7
3554:978-1-4614-9631-1
3172:10.1021/mp500426r
2625:10.1038/srep20031
2178:Molecular Therapy
2028:(14): 6505–6517.
1639:978-1-904455-25-7
1374:10.1002/wnan.1595
1052:978-1-4939-2290-1
697:administered RNAi
508:, and subsequent
353:expression vector
4780:
4735:
4734:
4712:Yeast
4533:Small temporal
4463:Piwi-interacting
4391:
4390:
4387:
4368:Deoxynucleotides
4331:
4324:
4317:
4308:
4307:
4069:
4062:
4055:
4046:
4045:
4035:
4025:
3984:
3929:
3928:
3926:
3924:
3910:
3904:
3903:
3901:
3899:
3885:
3879:
3878:
3868:
3858:
3834:
3828:
3827:
3820:
3814:
3813:
3811:
3809:
3794:
3788:
3787:
3777:
3737:
3731:
3730:
3720:
3688:
3682:
3681:
3647:
3641:
3640:
3630:
3598:
3592:
3591:
3573:
3567:
3566:
3532:
3526:
3525:
3518:
3512:
3511:
3503:
3497:
3496:
3486:
3454:
3448:
3447:
3445:
3443:
3428:
3422:
3421:
3410:10.1038/nmat3765
3385:
3376:
3375:
3365:
3347:
3323:
3317:
3316:
3306:
3274:
3268:
3267:
3257:
3242:Cancer Discovery
3233:
3227:
3226:
3219:
3213:
3212:
3200:
3194:
3193:
3183:
3166:(10): 3395–408.
3151:
3145:
3144:
3123:
3110:
3109:
3099:
3089:
3065:
3059:
3058:
3048:
3016:
3010:
3009:
2999:
2967:
2956:
2955:
2945:
2913:
2898:
2897:
2887:
2855:
2842:
2841:
2805:
2792:
2791:
2773:
2749:
2743:
2742:
2732:
2722:
2698:
2692:
2691:
2673:
2653:
2647:
2646:
2636:
2596:
2590:
2589:
2556:(7092): 537–41.
2545:
2539:
2538:
2528:
2517:10.1038/nbt.1543
2496:
2490:
2489:
2479:
2447:
2441:
2440:
2430:
2413:(9): 2931–2943.
2396:
2390:
2389:
2370:10.1038/nmeth854
2353:
2347:
2346:
2310:
2304:
2303:
2293:
2261:
2255:
2254:
2218:
2212:
2211:
2201:
2169:
2163:
2162:
2152:
2142:
2110:
2101:
2100:
2064:
2058:
2057:
2047:
2037:
2013:
2004:
2003:
1993:
1969:Current Genomics
1959:
1953:
1952:
1916:
1907:
1901:
1900:
1890:
1858:
1852:
1851:
1841:
1817:
1806:
1805:
1795:
1763:
1754:
1753:
1735:
1711:
1705:
1704:
1698:
1690:
1650:
1644:
1643:
1625:
1619:
1618:
1610:
1604:
1603:
1593:
1583:
1551:
1545:
1544:
1542:
1540:
1530:
1524:
1523:
1487:
1481:
1480:
1470:
1438:
1432:
1431:
1429:
1427:
1422:. 10 August 2018
1410:
1404:
1403:
1393:
1353:
1347:
1346:
1327:10.1038/35078107
1302:
1296:
1295:
1259:
1253:
1252:
1216:
1201:
1200:
1181:10.1038/35053110
1153:
1147:
1141:
1136:
1126:
1109:(9): 2931–2943.
1092:
1075:
1074:
1064:
1030:
748:RNA interference
243:drug development
220:and reported in
208:'s group at the
71:RNA interference
50:, is a class of
21:RNA interference
4788:
4787:
4783:
4782:
4781:
4779:
4778:
4777:
4748:
4747:
4746:
4741:
4723:
4664:Cloning vectors
4658:
4644:Locked
4608:
4558:
4547:
4506:
4434:
4381:
4380:
4372:
4341:
4335:
4305:
4300:
4274:
4255:Retrotransposon
4243:
4222:
4161:Gene regulation
4156:
4115:
4079:
4073:
4043:
4038:
3951:(7006): 371–8.
3938:
3936:Further reading
3933:
3932:
3922:
3920:
3912:
3911:
3907:
3897:
3895:
3887:
3886:
3882:
3835:
3831:
3822:
3821:
3817:
3807:
3805:
3795:
3791:
3738:
3734:
3689:
3685:
3670:
3648:
3644:
3599:
3595:
3588:
3574:
3570:
3555:
3533:
3529:
3520:
3519:
3515:
3504:
3500:
3469:(3–4): 224–32.
3455:
3451:
3441:
3439:
3433:"Transfection:
3429:
3425:
3396:(11): 967–977.
3386:
3379:
3324:
3320:
3275:
3271:
3234:
3230:
3221:
3220:
3216:
3201:
3197:
3152:
3148:
3124:
3113:
3080:(14): 5715–21.
3066:
3062:
3017:
3013:
2968:
2959:
2914:
2901:
2856:
2845:
2806:
2795:
2750:
2746:
2699:
2695:
2671:10.1.1.465.8240
2654:
2650:
2597:
2593:
2546:
2542:
2497:
2493:
2468:10.1038/nrg3978
2448:
2444:
2397:
2393:
2354:
2350:
2311:
2307:
2262:
2258:
2219:
2215:
2170:
2166:
2111:
2104:
2081:10.1038/nrd3010
2065:
2061:
2014:
2007:
1960:
1956:
1914:
1908:
1904:
1859:
1855:
1818:
1809:
1764:
1757:
1712:
1708:
1692:
1691:
1651:
1647:
1640:
1626:
1622:
1611:
1607:
1552:
1548:
1538:
1536:
1532:
1531:
1527:
1488:
1484:
1439:
1435:
1425:
1423:
1412:
1411:
1407:
1354:
1350:
1313:(6836): 494–8.
1303:
1299:
1270:(5441): 950–2.
1260:
1256:
1227:(7778): S4–S6.
1217:
1204:
1167:(6818): 363–6.
1154:
1150:
1093:
1078:
1053:
1031:
1027:
1022:
965:
947:partnered with
897:porphobilinogen
857:
823:
799:
787:
785:Electroporation
781:
779:Electroporation
760:
744:
738:
729:
713:Pharmacodynamic
627:pharmacokinetic
616:
596:
587:
578:
565:
556:
554:Innate immunity
539:
526:
518:heterochromatin
482:
416:
396:
330:
276:siRNA Mechanism
267:
255:innate immunity
206:David Baulcombe
199:transcriptional
189:. They won the
161:
107:
23:
17:
12:
11:
5:
4786:
4776:
4775:
4773:Non-coding RNA
4770:
4765:
4760:
4743:
4742:
4740:
4739:
4728:
4725:
4724:
4722:
4721:
4720:
4719:
4714:
4709:
4704:
4694:
4689:
4684:
4679:
4674:
4668:
4666:
4660:
4659:
4657:
4656:
4651:
4649:Peptide
4646:
4641:
4640:
4639:
4634:
4629:
4627:Glycol
4618:
4616:
4610:
4609:
4607:
4606:
4601:
4596:
4591:
4586:
4581:
4580:
4579:
4574:
4563:
4561:
4553:
4552:
4549:
4548:
4546:
4545:
4540:
4535:
4530:
4525:
4520:
4514:
4512:
4508:
4507:
4505:
4504:
4499:
4498:
4497:
4492:
4487:
4482:
4472:
4467:
4466:
4465:
4460:
4455:
4444:
4442:
4436:
4435:
4433:
4432:
4427:
4422:
4417:
4412:
4411:
4410:
4399:
4397:
4388:
4374:
4373:
4371:
4370:
4365:
4360:
4355:
4349:
4347:
4343:
4342:
4339:nucleic acids
4334:
4333:
4326:
4319:
4311:
4302:
4301:
4299:
4298:
4293:
4288:
4286:Telomerase RNA
4282:
4280:
4276:
4275:
4273:
4272:
4267:
4262:
4257:
4251:
4249:
4245:
4244:
4242:
4241:
4236:
4230:
4228:
4224:
4223:
4221:
4220:
4215:
4210:
4205:
4200:
4195:
4190:
4185:
4180:
4175:
4170:
4164:
4162:
4158:
4157:
4155:
4154:
4149:
4144:
4139:
4134:
4129:
4123:
4121:
4120:RNA processing
4117:
4116:
4114:
4113:
4108:
4103:
4098:
4093:
4087:
4085:
4081:
4080:
4072:
4071:
4064:
4057:
4049:
4042:
4041:External links
4039:
4037:
4036:
3985:
3939:
3937:
3934:
3931:
3930:
3918:BioPharma Dive
3905:
3880:
3829:
3815:
3789:
3732:
3683:
3668:
3642:
3593:
3586:
3568:
3553:
3527:
3513:
3498:
3449:
3423:
3377:
3318:
3269:
3228:
3214:
3195:
3146:
3111:
3060:
3031:(2): 188–200.
3011:
2957:
2899:
2843:
2793:
2744:
2693:
2664:(3): 594–605.
2648:
2591:
2540:
2491:
2442:
2391:
2364:(3): 199–204.
2358:Nature Methods
2348:
2305:
2276:(6): 489–513.
2256:
2213:
2184:(9): 1676–87.
2164:
2125:(16): 7305–9.
2102:
2059:
2005:
1976:(2): 508–518.
1954:
1902:
1853:
1807:
1755:
1706:
1645:
1638:
1620:
1605:
1546:
1525:
1482:
1433:
1405:
1348:
1297:
1254:
1202:
1148:
1076:
1051:
1024:
1023:
1021:
1018:
1017:
1016:
1011:
1006:
1001:
996:
991:
986:
981:
976:
974:Gene silencing
971:
969:Gene knockdown
964:
961:
932:(ALN-GO1) and
856:
853:
822:
819:
798:
795:
783:Main article:
780:
777:
759:
756:
752:immunogenicity
740:Main article:
737:
734:
728:
725:
695:to liver were
667:CNS) disorders
615:
612:
595:
592:
586:
583:
577:
574:
564:
561:
555:
552:
538:
535:
525:
522:
481:
478:
449:ATP hydrolysis
415:
412:
395:
394:RNA activation
392:
384:cell squeezing
345:Gene knockdown
338:protein domain
329:
326:
314:
313:
309:
302:
299:
296:
293:
286:
266:
263:
202:gene silencing
160:
157:
126:phosphorylated
106:
103:
101:in Worcester.
56:non-coding RNA
15:
9:
6:
4:
3:
2:
4785:
4774:
4771:
4769:
4766:
4764:
4761:
4759:
4756:
4755:
4753:
4738:
4730:
4729:
4726:
4718:
4715:
4713:
4710:
4708:
4705:
4703:
4700:
4699:
4698:
4695:
4693:
4690:
4688:
4685:
4683:
4680:
4678:
4675:
4673:
4670:
4669:
4667:
4665:
4661:
4655:
4652:
4650:
4647:
4645:
4642:
4638:
4635:
4633:
4632:Threose
4630:
4628:
4625:
4624:
4623:
4620:
4619:
4617:
4615:
4611:
4605:
4602:
4600:
4597:
4595:
4592:
4590:
4589:Deoxyribozyme
4587:
4585:
4582:
4578:
4577:Mitochondrial
4575:
4573:
4570:
4569:
4568:
4565:
4564:
4562:
4560:
4554:
4544:
4541:
4539:
4536:
4534:
4531:
4529:
4526:
4524:
4521:
4519:
4516:
4515:
4513:
4509:
4503:
4500:
4496:
4493:
4491:
4488:
4486:
4483:
4481:
4478:
4477:
4476:
4473:
4471:
4468:
4464:
4461:
4459:
4456:
4454:
4451:
4450:
4449:
4446:
4445:
4443:
4441:
4437:
4431:
4428:
4426:
4423:
4421:
4418:
4416:
4413:
4409:
4406:
4405:
4404:
4401:
4400:
4398:
4396:
4395:Translational
4392:
4389:
4385:
4379:
4375:
4369:
4366:
4364:
4361:
4359:
4356:
4354:
4351:
4350:
4348:
4344:
4340:
4332:
4327:
4325:
4320:
4318:
4313:
4312:
4309:
4297:
4294:
4292:
4289:
4287:
4284:
4283:
4281:
4277:
4271:
4268:
4266:
4263:
4261:
4258:
4256:
4253:
4252:
4250:
4246:
4240:
4239:SECIS element
4237:
4235:
4232:
4231:
4229:
4225:
4219:
4216:
4214:
4211:
4209:
4206:
4204:
4201:
4199:
4196:
4194:
4191:
4189:
4186:
4184:
4181:
4179:
4176:
4174:
4171:
4169:
4168:Antisense RNA
4166:
4165:
4163:
4159:
4153:
4150:
4148:
4145:
4143:
4140:
4138:
4135:
4133:
4130:
4128:
4125:
4124:
4122:
4118:
4112:
4109:
4107:
4104:
4102:
4099:
4097:
4096:Ribosomal RNA
4094:
4092:
4091:Messenger RNA
4089:
4088:
4086:
4082:
4078:
4070:
4065:
4063:
4058:
4056:
4051:
4050:
4047:
4033:
4029:
4024:
4019:
4015:
4011:
4007:
4003:
3999:
3995:
3991:
3986:
3982:
3978:
3974:
3970:
3966:
3962:
3958:
3954:
3950:
3946:
3941:
3940:
3919:
3915:
3909:
3894:
3890:
3884:
3876:
3872:
3867:
3862:
3857:
3852:
3848:
3844:
3840:
3833:
3825:
3819:
3804:
3800:
3793:
3785:
3781:
3776:
3771:
3767:
3763:
3759:
3755:
3751:
3747:
3743:
3736:
3728:
3724:
3719:
3714:
3710:
3706:
3703:(3): 142–51.
3702:
3698:
3694:
3687:
3679:
3675:
3671:
3665:
3661:
3657:
3653:
3646:
3638:
3634:
3629:
3624:
3620:
3616:
3612:
3608:
3604:
3597:
3589:
3583:
3579:
3572:
3564:
3560:
3556:
3550:
3546:
3542:
3538:
3531:
3523:
3517:
3509:
3502:
3494:
3490:
3485:
3480:
3476:
3472:
3468:
3464:
3460:
3453:
3438:
3437:Transfection"
3436:
3427:
3419:
3415:
3411:
3407:
3403:
3399:
3395:
3391:
3384:
3382:
3373:
3369:
3364:
3359:
3355:
3351:
3346:
3341:
3337:
3333:
3329:
3322:
3314:
3310:
3305:
3300:
3296:
3292:
3288:
3284:
3280:
3273:
3265:
3261:
3256:
3251:
3248:(4): 406–17.
3247:
3243:
3239:
3232:
3224:
3218:
3210:
3206:
3199:
3191:
3187:
3182:
3177:
3173:
3169:
3165:
3161:
3157:
3150:
3142:
3138:
3134:
3130:
3122:
3120:
3118:
3116:
3107:
3103:
3098:
3093:
3088:
3083:
3079:
3075:
3071:
3064:
3056:
3052:
3047:
3042:
3038:
3034:
3030:
3026:
3022:
3015:
3007:
3003:
2998:
2993:
2989:
2985:
2981:
2977:
2973:
2966:
2964:
2962:
2953:
2949:
2944:
2939:
2935:
2931:
2928:(6): 367–73.
2927:
2923:
2919:
2912:
2910:
2908:
2906:
2904:
2895:
2891:
2886:
2881:
2877:
2873:
2869:
2865:
2861:
2854:
2852:
2850:
2848:
2839:
2835:
2831:
2827:
2823:
2819:
2816:(6): 747–54.
2815:
2811:
2804:
2802:
2800:
2798:
2789:
2785:
2781:
2777:
2772:
2767:
2763:
2759:
2755:
2748:
2740:
2736:
2731:
2726:
2721:
2716:
2712:
2708:
2704:
2697:
2689:
2685:
2681:
2677:
2672:
2667:
2663:
2659:
2652:
2644:
2640:
2635:
2630:
2626:
2622:
2618:
2614:
2610:
2606:
2602:
2595:
2587:
2583:
2579:
2575:
2571:
2567:
2563:
2559:
2555:
2551:
2544:
2536:
2532:
2527:
2522:
2518:
2514:
2511:(6): 549–55.
2510:
2506:
2502:
2495:
2487:
2483:
2478:
2473:
2469:
2465:
2462:(9): 543–52.
2461:
2457:
2453:
2446:
2438:
2434:
2429:
2424:
2420:
2416:
2412:
2408:
2407:
2402:
2395:
2387:
2383:
2379:
2375:
2371:
2367:
2363:
2359:
2352:
2344:
2340:
2336:
2332:
2328:
2324:
2321:(2): 116–20.
2320:
2316:
2309:
2301:
2297:
2292:
2287:
2283:
2279:
2275:
2271:
2267:
2260:
2252:
2248:
2244:
2240:
2236:
2232:
2228:
2224:
2217:
2209:
2205:
2200:
2195:
2191:
2187:
2183:
2179:
2175:
2168:
2160:
2156:
2151:
2146:
2141:
2136:
2132:
2128:
2124:
2120:
2116:
2109:
2107:
2098:
2094:
2090:
2086:
2082:
2078:
2074:
2070:
2063:
2055:
2051:
2046:
2041:
2036:
2031:
2027:
2023:
2019:
2012:
2010:
2001:
1997:
1992:
1987:
1983:
1979:
1975:
1971:
1970:
1965:
1958:
1950:
1946:
1942:
1938:
1934:
1930:
1927:(2): 89–108.
1926:
1922:
1921:
1913:
1906:
1898:
1894:
1889:
1884:
1880:
1876:
1873:(4): 459–69.
1872:
1868:
1864:
1857:
1849:
1845:
1840:
1835:
1832:(5): 517–29.
1831:
1827:
1823:
1816:
1814:
1812:
1803:
1799:
1794:
1789:
1785:
1781:
1778:(4): 642–55.
1777:
1773:
1769:
1762:
1760:
1751:
1747:
1743:
1739:
1734:
1729:
1725:
1721:
1717:
1710:
1702:
1696:
1688:
1684:
1680:
1676:
1672:
1668:
1664:
1660:
1656:
1649:
1641:
1635:
1631:
1624:
1616:
1609:
1601:
1597:
1592:
1587:
1582:
1577:
1573:
1569:
1566:(6): 2082–7.
1565:
1561:
1557:
1550:
1535:
1529:
1521:
1517:
1513:
1509:
1505:
1501:
1497:
1493:
1486:
1478:
1474:
1469:
1464:
1460:
1456:
1452:
1448:
1444:
1437:
1421:
1420:
1415:
1409:
1401:
1397:
1392:
1387:
1383:
1379:
1375:
1371:
1367:
1363:
1359:
1352:
1344:
1340:
1336:
1332:
1328:
1324:
1320:
1316:
1312:
1308:
1301:
1293:
1289:
1285:
1281:
1277:
1273:
1269:
1265:
1258:
1250:
1246:
1242:
1238:
1234:
1230:
1226:
1222:
1215:
1213:
1211:
1209:
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1198:
1194:
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1186:
1182:
1178:
1174:
1170:
1166:
1162:
1158:
1152:
1145:
1140:
1134:
1130:
1125:
1120:
1116:
1112:
1108:
1104:
1103:
1098:
1091:
1089:
1087:
1085:
1083:
1081:
1072:
1068:
1063:
1058:
1054:
1048:
1044:
1040:
1036:
1029:
1025:
1015:
1012:
1010:
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1005:
1002:
1000:
997:
995:
992:
990:
987:
985:
982:
980:
977:
975:
972:
970:
967:
966:
960:
958:
954:
950:
946:
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937:
935:
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926:
924:
920:
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912:
907:
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900:
898:
894:
889:
887:
881:
877:
874:
870:
866:
862:
852:
850:
845:
841:
836:
833:
828:
818:
816:
811:
809:
805:
794:
791:
786:
776:
774:
773:Lipofectamine
771:of siRNA are
770:
766:
755:
753:
749:
743:
733:
724:
720:
718:
714:
710:
706:
702:
698:
694:
689:
687:
682:
678:
676:
672:
668:
664:
659:
657:
653:
647:
645:
640:
636:
632:
631:nanoparticles
628:
623:
621:
611:
609:
600:
591:
582:
573:
571:
563:Off-targeting
560:
551:
549:
545:
534:
530:
521:
519:
515:
511:
507:
503:
499:
496:) and worms (
495:
491:
487:
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474:
470:
464:
460:
458:
452:
450:
446:
442:
438:
434:
430:
425:
421:
411:
409:
408:Aedes aegypti
405:
401:
391:
387:
385:
380:
378:
374:
370:
366:
362:
358:
354:
350:
346:
339:
334:
325:
323:
319:
310:
307:
303:
300:
297:
294:
291:
287:
284:
280:
279:
274:
270:
262:
258:
256:
252:
248:
247:nanoparticles
244:
240:
235:
234:
229:
228:Thomas Tuschl
225:
224:
219:
215:
211:
207:
203:
200:
196:
192:
188:
187:
182:
178:
174:
170:
166:
156:
154:
150:
146:
142:
138:
135:
131:
127:
124:(dsRNA) with
123:
119:
111:
102:
100:
96:
92:
88:
84:
81:, preventing
80:
79:transcription
76:
72:
68:
64:
60:
57:
53:
49:
48:silencing RNA
45:
41:
37:
29:
25:
22:
4707:Bacterial
4682:Lambda phage
4457:
4346:Constituents
4296:List of RNAs
4202:
4106:Transfer RNA
3997:
3993:
3948:
3944:
3921:. Retrieved
3917:
3908:
3896:. Retrieved
3892:
3883:
3849:(1): 11–21.
3846:
3842:
3832:
3818:
3806:. Retrieved
3802:
3792:
3749:
3745:
3735:
3700:
3696:
3686:
3651:
3645:
3613:(6): 553–8.
3610:
3607:Gene Therapy
3606:
3596:
3577:
3571:
3536:
3530:
3516:
3507:
3501:
3466:
3462:
3452:
3440:. Retrieved
3434:
3426:
3393:
3389:
3335:
3331:
3321:
3286:
3282:
3272:
3245:
3241:
3231:
3217:
3208:
3198:
3163:
3159:
3149:
3132:
3128:
3077:
3073:
3063:
3028:
3024:
3014:
2982:(1): 60–71.
2979:
2975:
2925:
2921:
2867:
2863:
2813:
2809:
2761:
2757:
2747:
2710:
2706:
2696:
2661:
2657:
2651:
2611:(1): 20031.
2608:
2604:
2594:
2553:
2549:
2543:
2508:
2504:
2494:
2459:
2455:
2445:
2410:
2404:
2394:
2361:
2357:
2351:
2318:
2314:
2308:
2273:
2269:
2259:
2229:(1): 77–96.
2226:
2222:
2216:
2181:
2177:
2167:
2122:
2118:
2075:(1): 57–67.
2072:
2068:
2062:
2025:
2021:
1973:
1967:
1957:
1924:
1918:
1905:
1870:
1866:
1856:
1829:
1825:
1775:
1771:
1726:(1): 69–81.
1723:
1719:
1709:
1695:cite journal
1662:
1658:
1648:
1629:
1623:
1614:
1608:
1563:
1559:
1549:
1537:. Retrieved
1528:
1498:(6): 631–8.
1495:
1491:
1485:
1450:
1446:
1436:
1424:. Retrieved
1417:
1408:
1368:(2): e1595.
1365:
1361:
1351:
1310:
1306:
1300:
1267:
1263:
1257:
1224:
1220:
1164:
1160:
1151:
1106:
1100:
1034:
1028:
938:
927:
908:
901:
890:
882:
878:
858:
837:
832:Watson-Crick
824:
812:
800:
792:
788:
769:transfection
761:
758:Transfection
745:
730:
721:
715:analysis of
693:metastasised
690:
683:
679:
660:
656:cyclodextrin
648:
624:
617:
604:
588:
579:
566:
557:
540:
531:
527:
483:
471:
469:
457:endonuclease
453:
429:exonucleases
417:
407:
397:
388:
381:
371:; H1 is the
369:RNA splicing
349:transfection
343:
315:
268:
259:
232:
222:
184:
162:
153:knocked down
149:transfection
130:hydroxylated
128:5' ends and
115:
47:
43:
39:
35:
34:
24:
4702:P1-derived
4470:Antisense
4363:Nucleotides
4358:Nucleosides
4353:Nucleobases
4000:(1): 1809.
3866:2445/138257
1157:Bernstein E
957:AstraZeneca
911:amyloidosis
873:amyloidosis
606:curated as
322:translation
191:Nobel prize
173:Craig Mello
165:Andrew Fire
95:Craig Mello
87:Andrew Fire
83:translation
16:Biomolecule
4752:Categories
4654:Morpholino
4567:Organellar
4475:Processual
4440:Regulatory
4384:non-coding
4234:Riboswitch
4178:CRISPR RNA
3442:5 December
2870:(1): 101.
2764:: 105310.
1665:: 103325.
1453:: bau103.
1020:References
999:VIRsiRNAdb
934:inclisiran
808:lentivirus
804:adenovirus
681:function.
498:C. elegans
492:), flies (
488:), yeast (
357:transcript
75:expression
63:base pairs
19:See also:
4614:Analogues
4599:Hachimoji
4382:(coding,
4337:Types of
4291:Vault RNA
4265:RNA virus
4248:Parasites
4147:RNase MRP
4137:Guide RNA
4075:Types of
3766:0169-409X
3752:: 64–78.
3390:Nat Mater
3354:2296-858X
2780:1567-7257
2713:(1): 45.
2666:CiteSeerX
1687:210891954
1382:1939-5116
1249:204741280
1014:Persomics
1009:Dharmacon
930:lumasiran
859:In 2018,
821:Therapies
644:membranes
544:microRNAs
424:Argonaute
308:cleavage.
265:Mechanism
226:in 1999.
163:In 1998,
105:Structure
59:molecules
54:at first
4737:Category
4672:Phagemid
4523:Ribozyme
4188:MicroRNA
4032:32286269
3973:15372045
3875:29972753
3784:32768564
3727:20049714
3678:23754221
3637:16397511
3563:24510818
3493:24598124
3435:In Vitro
3418:24150415
3372:36325384
3313:20511019
3264:23358650
3190:25157701
3135:: 8–15.
3106:17379663
3055:11157775
3006:22284355
2952:22555511
2894:32561705
2838:15337692
2830:21079135
2788:35636695
2739:19439102
2688:17914454
2643:26818131
2586:15118504
2578:16724069
2535:19465925
2486:26281785
2437:28696921
2386:52809577
2378:16489337
2343:24309609
2335:20119685
2300:21175414
2251:28803811
2243:22432611
2208:21673662
2097:20903257
2089:20043028
2054:27060137
2000:32655289
1949:53565676
1941:30446728
1897:15703439
1848:15741316
1802:19239886
1742:15066283
1679:31978586
1600:23341631
1520:35357127
1512:17557095
1477:25380780
1447:Database
1426:26 March
1400:31642207
1335:11373684
1292:17480249
1284:10542148
1189:11201747
1133:28696921
1071:25577393
989:NatsiRNA
963:See also
608:siRNAmod
4677:Plasmid
4142:RNase P
4023:7156650
4002:Bibcode
3981:4410723
3953:Bibcode
3775:7406478
3718:3378126
3628:7091755
3484:3988888
3398:Bibcode
3363:9618588
3304:7138079
3181:4186677
3097:1829492
2997:3269031
2943:3842228
2885:7305320
2730:2686705
2634:4730238
2613:Bibcode
2558:Bibcode
2526:2782465
2477:4756474
2428:5592921
2291:3099591
2199:3182346
2159:1380154
2127:Bibcode
2045:5001580
1991:7327968
1888:1370735
1793:2675692
1750:6683459
1591:3568376
1568:Bibcode
1539:27 July
1468:4224276
1391:7360334
1315:Bibcode
1264:Science
1229:Bibcode
1197:4371481
1169:Bibcode
1124:5592921
1062:4425273
437:exosome
223:Science
218:England
214:Norwich
159:History
4692:Fosmid
4687:Cosmid
4637:Hexose
4559:acids
4511:Others
4270:Viroid
4030:
4020:
3979:
3971:
3945:Nature
3923:24 May
3898:24 May
3873:
3808:24 May
3782:
3772:
3764:
3725:
3715:
3676:
3666:
3635:
3625:
3584:
3561:
3551:
3491:
3481:
3416:
3370:
3360:
3352:
3311:
3301:
3283:Lancet
3262:
3209:SFGATE
3188:
3178:
3104:
3094:
3053:
3046:312613
3043:
3004:
2994:
2950:
2940:
2892:
2882:
2836:
2828:
2786:
2778:
2737:
2727:
2686:
2668:
2641:
2631:
2584:
2576:
2550:Nature
2533:
2523:
2484:
2474:
2435:
2425:
2384:
2376:
2341:
2333:
2298:
2288:
2249:
2241:
2206:
2196:
2157:
2147:
2095:
2087:
2052:
2042:
1998:
1988:
1947:
1939:
1895:
1885:
1846:
1800:
1790:
1748:
1740:
1685:
1677:
1636:
1598:
1588:
1518:
1510:
1475:
1465:
1398:
1388:
1380:
1343:710341
1341:
1333:
1307:Nature
1290:
1282:
1247:
1221:Nature
1195:
1187:
1161:Nature
1131:
1121:
1069:
1059:
1049:
1004:CRISPR
994:Viroid
984:EsiRNA
806:, and
717:biopsy
635:oligos
441:5' end
433:3' end
233:Nature
141:dsRNAs
137:enzyme
4717:Human
4495:Y RNA
4279:Other
4152:Y RNA
3977:S2CID
2834:S2CID
2582:S2CID
2382:S2CID
2339:S2CID
2247:S2CID
2150:49698
2093:S2CID
1945:S2CID
1915:(PDF)
1746:S2CID
1683:S2CID
1516:S2CID
1339:S2CID
1288:S2CID
1245:S2CID
1193:S2CID
953:Amgen
675:brain
652:Lipid
377:Dicer
373:RNase
361:Dicer
318:miRNA
312:mRNA.
283:Dicer
134:Dicer
67:miRNA
40:siRNA
4028:PMID
3969:PMID
3925:2021
3900:2021
3871:PMID
3810:2021
3780:PMID
3762:ISSN
3723:PMID
3674:PMID
3664:ISBN
3633:PMID
3582:ISBN
3559:PMID
3549:ISBN
3489:PMID
3444:2017
3414:PMID
3368:PMID
3350:ISSN
3309:PMID
3260:PMID
3186:PMID
3102:PMID
3051:PMID
3002:PMID
2948:PMID
2890:PMID
2826:PMID
2784:PMID
2776:ISSN
2735:PMID
2684:PMID
2639:PMID
2574:PMID
2531:PMID
2482:PMID
2433:PMID
2374:PMID
2331:PMID
2296:PMID
2239:PMID
2204:PMID
2155:PMID
2085:PMID
2050:PMID
1996:PMID
1937:PMID
1893:PMID
1844:PMID
1798:PMID
1772:Cell
1738:PMID
1720:Cell
1701:link
1675:PMID
1634:ISBN
1596:PMID
1541:2018
1508:PMID
1473:PMID
1451:2014
1428:2021
1396:PMID
1378:ISSN
1331:PMID
1280:PMID
1185:PMID
1129:PMID
1067:PMID
1047:ISBN
955:and
943:and
917:and
827:RNAi
705:VEGF
620:RNAi
548:mRNA
445:XRN1
400:RNAa
306:mRNA
290:RISC
241:and
195:RNAi
181:RNAi
143:and
4758:RNA
4077:RNA
4018:PMC
4010:doi
3961:doi
3949:431
3861:hdl
3851:doi
3847:379
3803:FDA
3770:PMC
3754:doi
3750:154
3713:PMC
3705:doi
3656:doi
3623:PMC
3615:doi
3541:doi
3479:PMC
3471:doi
3467:158
3406:doi
3358:PMC
3340:doi
3299:PMC
3291:doi
3287:375
3250:doi
3176:PMC
3168:doi
3137:doi
3133:503
3092:PMC
3082:doi
3078:104
3041:PMC
3033:doi
2992:PMC
2984:doi
2938:PMC
2930:doi
2880:PMC
2872:doi
2818:doi
2766:doi
2762:102
2725:PMC
2715:doi
2676:doi
2662:128
2629:PMC
2621:doi
2566:doi
2554:441
2521:PMC
2513:doi
2472:PMC
2464:doi
2423:PMC
2415:doi
2366:doi
2323:doi
2286:PMC
2278:doi
2231:doi
2194:PMC
2186:doi
2145:PMC
2135:doi
2077:doi
2040:PMC
2030:doi
1986:PMC
1978:doi
1929:doi
1883:PMC
1875:doi
1867:RNA
1834:doi
1788:PMC
1780:doi
1776:136
1728:doi
1724:117
1667:doi
1663:119
1586:PMC
1576:doi
1564:110
1500:doi
1463:PMC
1455:doi
1386:PMC
1370:doi
1323:doi
1311:411
1272:doi
1268:286
1237:doi
1225:574
1177:doi
1165:409
1119:PMC
1111:doi
1057:PMC
1039:doi
865:FDA
849:RNA
709:KSP
435:by
347:by
212:in
175:at
167:at
97:at
89:at
46:or
4754::
4026:.
4016:.
4008:.
3998:11
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3967:.
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3609:.
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3461:.
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3394:12
3392:.
3380:^
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3330:.
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3114:^
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3076:.
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3049:.
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3023:.
3000:.
2990:.
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2960:^
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2832:.
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