How does rna silencing work

Many of these solutions need to be very specific to individual cell types. He notes, however, that if Arrowhead figures out what modifications a molecule needs to target a given cell population, the exercise opens the possibility of manipulating any genes in that cell population.

In the RNAi space, Arrowhead has pioneered potential treatments for hypertriglyceridemia. The company is the sole owner of two clinical programs that are intended for this metabolic dysregulation.

Arrowhead has also developed the first clear cell renal cell carcinoma tumor targeting program. It has yielded a drug candidate, ARO-HIF2, that inhibits the production of HIF-2a, which is linked to tumor progression and metastasis and is overexpressed in most clear cell renal cell cancers. RNAi therapeutics are still maturing, but they have already shown promise in drug development programs, particularly with respect to safety and toleration profiles.

In addition to the in-house programs, Dicerna recently initiated five major research and development collaborations. Log in to leave a comment. Sign in. Forgot your password? Get help. Privacy Policy. Create an account. Password recovery. All Trends for Trends for Identifying the Next Frontier in Vaccine Manufacturing. Educating Next-Generation Bioprocess Engineers. European Molecular Biology Organization Journal , , vol. RNA as a target and an initiator of posttranscriptional gene silencing in transgenic plants.

Plant Molecular Biology , , vol. A branched pathway for transgene-induced RNA silencing in plants. Current Biology , , vol. Genetics , , vol. Biochemical Biophysical Acta , , vol. The Argonaute family: tentacles that reach into RNAi, developmental control, stem cell maintenance, and tumorigenesis.

Genes and Development , , vol. Gene silencing by double-stranded RNA. Current Opinion in Genetics and Development , , vol. Post-transcriptional gene silencing across kingdoms.

Science , , vol. Breakthrough of the year. Small RNAs make big splash. A novel class of evolutionarily conserved genes defined by piwi are essential for stem cell self-renewal. An RNA-dependent RNA polymerase gene in Arabidopsis is required for post-transcriptional gene silencing mediated by a transgene but not by a virus. Cell , , vol. RNA-triggered gene silencing. Trends in Genetics , , vol. Potent and specific genetic interference by double-stranded RNA in C.

Nature , , vol. European Molecular Biology Organization journal, , vol. A species of small antisense RNA in posttranscriptional gene silencing in plants. A touch of elegance with RNAi. RNA-directed transcriptional gene silencing in plants can be inherited independently of the RNA trigger and requires Met-1 for maintenance. Development and Cell , , vol. A genetic link between co-suppression and RNA interference in C.

Mut-7 of C. Molecular mechanism of RNA silencing suppression mediated by p19 protein of tombusviruses. European Molecular Biology Organisation Journal , , vol.

Double-stranded RNA injection produces null phenotypes in zebrafish. Developmental Biology , , vol. Endogenous and silencing-associated small RNAs in plants. Plant Cell , , vol. HC-Pro suppression of gene silencing eliminates the small RNAs but not transgene methylation or the mobile signal.

RNA: guiding gene silencing. How and why do plants inactivate homologous transgenes? Plant Physiology , , vol. Transcriptional gene silencing and promoter methylation triggered by dsRNA. Comparison of the suppressive effects of antisense oligonucleotides and siRNAs directed against the same targets in mammalian cells.

Antisense Nucleic Acid Drug Development , , vol. Double-stranded RNA as a mediator in sequence-specific genetic silencing and co-suppression.

Trends in Genetics, , vol. Cell, , vol. The silence of the genes. The nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Two genetic circuits repress the Caenorhabditis elegans heterochronic gene lin after translation initiation.

RNAi: gene-silencing in therapeutic intervention. Drug Discovery Today , , vol. FEMS Microbiol. Fabozzi, G. Ebolavirus proteins suppress the effects of small interfering RNA by direct interaction with the mammalian RNA interference pathway.

Fire, A. Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Flisiak, R. Expert Opin. Ge, Q. Geisbert, T. Postexposure protection of non-human primates against a lethal Ebola virus challenge with RNA interference: a proof-of-concept study. Lancet , — Gimenez-Barcons, M. Endoribonuclease-prepared short interfering RNAs induce effective and specific inhibition of human immunodeficiency virus type 1 replication.

Gish, R. Gitlin, L. Short interfering RNA confers intracellular antiviral immunity in human cells. Poliovirus escape from RNA interference: short interfering RNA-target recognition and implications for therapeutic approaches.

Gottlieb, J. ALN-RSV01 for prevention of bronchiolitis obliterans syndrome after respiratory syncytial virus infection in lung transplant recipients. Heart Lung Transplant. Hannus, M. Heninger, A. Production of endoribonuclease-prepared short interfering RNAs esiRNAs for specific and effective gene silencing in mammalian cells. CSH Protoc. Huang, L. Production of highly potent recombinant siRNAs in Escherichia coli. Jacque, J. Kaczmarek, J.

Advances in the delivery of RNA therapeutics: from concept to clinical reality. Kapadia, S. Kim, D. Kok, K. Cell Host Microbe 9, — Kraft, C. The use of TKM and convalescent plasma in 2 patients with ebola virus disease in the United States. Kumar, P. Cell , — Macrae, I. Structural basis for double-stranded RNA processing by Dicer. Maillard, P. EMBO J. Makeyev, E.

Replicase activity of purified recombinant protein P2 of double-stranded RNA bacteriophage phi6. Minks, M. Structural requirements of double-stranded RNA for the activation of 2',5'-oligo A polymerase and protein kinase of interferon-treated HeLa cells.

Morrissey, D. Musacchio, T. Nair, J. Naso, M. Adeno-associated virus AAV as a vector for gene therapy. BioDrugs 31, — Niehl, A. Synthetic biology approach for plant protection using dsRNA.

Plant Biotechnol. Olejniczak, M. Recent advances in understanding of the immunological off-target effects of siRNA. Gene Ther. Paavilainen, H. Inhibition of clinical pathogenic herpes simplex virus 1 strains with enzymatically created siRNA pools. Topical treatment of herpes simplex virus infection with enzymatically created siRNA swarm. Palliser, D.

An siRNA-based microbicide protects mice from lethal herpes simplex virus 2 infection. Nature , 89— Pozzi, D.

Mechanistic evaluation of the transfection barriers involved in lipid-mediated gene delivery: interplay between nanostructure and composition.

Acta , — Qiu, Y. Human virus-derived small RNAs can confer antiviral immunity in mammals. Immunity 46, — Randall, G. Reynolds, A. Rohayem, J. Romanovskaya, A. Enzymatically produced pools of canonical and Dicer-substrate siRNA molecules display comparable gene silencing and antiviral activities against herpes simplex virus.

High-throughput purification of double-stranded RNA molecules using convective interaction media monolithic anion exchange columns. A , 54— Rozema, D. Scarborough, R. Viruses E8. Schluep, T.