ArticleAIDS research and therapy2011
Multiple shRNA combinations for near-complete coverage of all HIV-1 strains.
Article in AIDS research and therapy, 2011. 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.
- Therapeutic Approaches of Viral Gene Silencing by Small Interfering RNA: Strategies to Prevent the Emergence of Antiviral Resistant Escape Mutants.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Multiplexed shRNA-miRs as a candidate for anti HIV-1 therapy: strategies, challenges, and future potential.Journal, genetic engineering & biotechnology · 2022Review
- CRISPR-Cas13a Inhibits HIV-1 Infection.Molecular therapy. Nucleic acids · 2020Article
- Article
- Recent advances in RNAi-based strategies for therapy and prevention of HIV-1/AIDS.Advanced drug delivery reviews · 2016Review
- Multiplexing seven miRNA-Based shRNAs to suppress HIV replication.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
- RNA interference approaches for treatment of HIV-1 infection.Genome medicine · 2015Article
- Safe, long-term hepatic expression of anti-HCV shRNA in a nonhuman primate model.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- HIV develops indirect cross-resistance to combinatorial RNAi targeting two distinct and spatially distant sites.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- In vitro characterization of the activity of PF-05095808, a novel biological agent for hepatitis C virus therapy.Antimicrobial agents and chemotherapy · 2012Article
- Antiviral RNAi: translating science towards therapeutic success.Pharmaceutical research · 2011Review
- HIVsirDB: a database of HIV inhibiting siRNAs.PloS one · 2011Article
Corrections and comments
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundCombinatorial RNA interference (co-RNAi) approaches are needed to account for viral variability in treating HIV-1 with RNAi, as single short hairpin RNAs (shRNA) are rapidly rendered ineffective by resistant strains. Current work suggests that 4 simultaneously expressed shRNAs may prevent the emergence of resistant strains.
resultsIn this study we assembled combinations of highly-conserved shRNAs to target as many HIV-1 strains as possible. We analyzed intersecting conservations of 10 shRNAs to find combinations with 4+ matching the maximum number of strains using 1220+ HIV-1 sequences from the Los Alamos National Laboratory (LANL). We built 26 combinations of 2 to 7 shRNAs with up to 87% coverage for all known strains and 100% coverage of clade B subtypes, and characterized their intrinsic suppressive activities in transient expression assays. We found that all combinations had high combined suppressive activities, though there were also large changes in the individual activities of the component shRNAs in our multiple expression cassette configurations.
conclusionBy considering the intersecting conservations of shRNA combinations we have shown that it is possible to assemble combinations of 6 and 7 highly active, highly conserved shRNAs such that there is always at least 4 shRNAs within each combination covering all currently known variants of entire HIV-1 subtypes. By extension, it may be possible to combine several combinations for complete global coverage of HIV-1 variants.
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Registered trials
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