AI Article Synopsis
- Combinatorial RNA interference (co-RNAi) is explored as a strategy to effectively combat HIV-1 by using multiple short hairpin RNAs (shRNAs) simultaneously to counteract viral resistance.
- The research identified combinations of highly-conserved shRNAs that target a range of HIV-1 strains using data from over 1,220 sequences, resulting in combinations that provide up to 87% coverage of known strains and 100% coverage of clade B subtypes.
- The findings suggest that it is feasible to create combinations of up to 7 shRNAs that maintain effective activity against diverse HIV-1 variants, potentially leading to broader treatment options against the virus.
Article Abstract
Background: Combinatorial 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.
Results: In 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.
Conclusion: By 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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| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033792 | PMC |
| http://dx.doi.org/10.1186/1742-6405-8-1 | DOI Listing |
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