ArticleMolecular therapy. Nucleic acids2014
Deep Sequencing Insights in Therapeutic shRNA Processing and siRNA Target Cleavage Precision.
Article in Molecular therapy. Nucleic acids, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 24 citations in OpenAlex.
- Analysis of Processing, Post-Maturation, and By-Products of shRNA in Gene and Cell Therapy Applications.Methods and protocols · 2025Article
- BB-301: a silence and replace AAV-based vector for the treatment of oculopharyngeal muscular dystrophy.Molecular therapy. Nucleic acids · 2021Article
- Comprehensive analysis of drugs to treat SARS‑CoV‑2 infection: Mechanistic insights into current COVID‑19 therapies (Review).International journal of molecular medicine · 2020Review
- Improved Nucleic Acid Therapy with Advanced Nanoscale Biotechnology.Molecular therapy. Nucleic acids · 2020Review
- Short Hairpin RNAs for Strand-Specific Small Interfering RNA Production.Frontiers in bioengineering and biotechnology · 2020Article
- Systematic sequencing of chloroplast transcript termini from Arabidopsis thaliana reveals >200 transcription initiation sites and the extensive imprints of RNA-binding proteins and secondary structures.Nucleic acids research · 2019Article
- Profiling the Mismatch Tolerance of Argonaute 2 through Deep Sequencing of Sliced Polymorphic Viral RNAs.Molecular therapy. Nucleic acids · 2017Article
- Dicer-independent processing of small RNA duplexes: mechanistic insights and applications.Nucleic acids research · 2017Review
- Quantitative evaluation of first, second, and third generation hairpin systems reveals the limit of mammalian vector-based RNAi.RNA biology · 2016Article
- Deep Sequence Analysis of AgoshRNA Processing Reveals 3' A Addition and Trimming.Molecular therapy. Nucleic acids · 2015Article
- Mechanistic insights on the Dicer-independent AGO2-mediated processing of AgoshRNAs.RNA biology · 2015Article
- Towards Antiviral shRNAs Based on the AgoshRNA Design.PloS one · 2015Article
Corrections and comments
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
TT-034 (PF-05095808) is a recombinant adeno-associated virus serotype 8 (AAV8) agent expressing three short hairpin RNA (shRNA) pro-drugs that target the hepatitis C virus (HCV) RNA genome. The cytosolic enzyme Dicer cleaves each shRNA into multiple, potentially active small interfering RNA (siRNA) drugs. Using next-generation sequencing (NGS) to identify and characterize active shRNAs maturation products, we observed that each TT-034-encoded shRNA could be processed into as many as 95 separate siRNA strands. Few of these appeared active as determined by Sanger 5' RNA Ligase-Mediated Rapid Amplification of cDNA Ends (5-RACE) and through synthetic shRNA and siRNA analogue studies. Moreover, NGS scrutiny applied on 5-RACE products (RACE-seq) suggested that synthetic siRNAs could direct cleavage in not one, but up to five separate positions on targeted RNA, in a sequence-dependent manner. These data support an on-target mechanism of action for TT-034 without cytotoxicity and question the accepted precision of substrate processing by the key RNA interference (RNAi) enzymes Dicer and siRNA-induced silencing complex (siRISC).Molecular Therapy-Nucleic Acids (2014) 3, e145; doi:10.1038/mtna.2013.73; published online 4 February 2014.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.