ArticleRetrovirology2009
96 shRNAs designed for maximal coverage of HIV-1 variants.
Article in Retrovirology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 47 citations in OpenAlex.
- A dual recombinant strategy to quantify PreS1 antibody in hepatitis B patients with genotype B or C virus by ELISA.iScience · 2026Article
- Editing out HIV: application of gene editing technology to achieve functional cure.Retrovirology · 2021Review
- Antiviral efficacy of short-hairpin RNAs and artificial microRNAs targeting foot-and-mouth disease virus.PeerJ · 2021Article
- RNA Interference Therapies for an HIV-1 Functional Cure.Viruses · 2017Review
- Efficacy Analysis of Combinatorial siRNAs against HIV Derived from One Double Hairpin RNA Precursor.Frontiers in microbiology · 2017Article
- Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy.Journal of visualized experiments : JoVE · 2016Article
- Design of Effective Primary MicroRNA Mimics With Different Basal Stem Conformations.Molecular therapy. Nucleic acids · 2016Article
- Effective inhibition of HIV-1 production by short hairpin RNAs and small interfering RNAs targeting a highly conserved site in HIV-1 Gag RNA is optimized by evaluating alternative length formats.Antimicrobial agents and chemotherapy · 2015Article
- Ectopic expression of anti-HIV-1 shRNAs protects CD8(+) T cells modified with CD4ζ CAR from HIV-1 infection and alleviates impairment of cell proliferation.Biochemical and biophysical research communications · 2015Article
- A Conserved Target Site in HIV-1 Gag RNA is Accessible to Inhibition by Both an HDV Ribozyme and a Short Hairpin RNA.Molecular therapy. Nucleic acids · 2014Article
- Silencing of HIV-1 gag gene from epidemic strains among men who have sex with men (MSM) in Tianjin, China by a broad-spectrum short hairpin RNA.Virusdisease · 2014Article
- Highly significant antiviral activity of HIV-1 LTR-specific tre-recombinase in humanized mice.PLoS pathogens · 2013Article
- Selection of RNAi-based inhibitors for anti-HIV gene therapy.World journal of virology · 2012Review
- SHAPE-directed discovery of potent shRNA inhibitors of HIV-1.Molecular therapy : the journal of the American Society of Gene Therapy · 2012Article
- Engineering HIV-1-resistant T-cells from short-hairpin RNA-expressing hematopoietic stem/progenitor cells in humanized BLT mice.PloS one · 2012Article
- A comparison of multiple shRNA expression methods for combinatorial RNAi.Genetic vaccines and therapy · 2011Article
- Multiple shRNA combinations for near-complete coverage of all HIV-1 strains.AIDS research and therapy · 2011Article
- HIVsirDB: a database of HIV inhibiting siRNAs.PloS one · 2011Article
- An RNAi in silico approach to find an optimal shRNA cocktail against HIV-1.Virology journal · 2010Article
- In silico modeling indicates the development of HIV-1 resistance to multiple shRNA gene therapy differs to standard antiretroviral therapy.Retrovirology · 2010Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe RNA interference (RNAi) pathway is a mechanism of gene-suppression with potential gene therapy applications for treating viral disease such as HIV-1. The most suitable inducer of RNAi for this application is short hairpin RNA (shRNA) although it is limited to suppressing a single target. A successful anti-HIV-1 therapy will require combinations of multiple highly active, highly conserved shRNAs to adequately counter the emergence of resistant strains.
resultsWe calculated the percentage conservations of 8, 846 unique 19 nucleotide HIV-1 targets amongst 37, 949 HIV-1 gene sequence fragments containing 24.8 million 19 mers. We developed a novel method of determining conservation in 'profile' sets of 5 overlapping 19 mer sequences (covering 23 nucleotides in total) to ensure that the intended conservation of each shRNA would be unaffected by possible variations in shRNA processing. Ninety six of the top ranking targets from 22 regions were selected based on conservation profiles, predicted activities, targets and specific nucleotide inclusion/exclusion criteria. We constructed 53 shRNAs with 20 bp stems and 43 shRNAs with 21 bp stems which we tested and ranked using fluorescent reporter and HIV-1 expression assays. Average suppressive activities ranged from 71 - 75%, with 65 hairpins classed as highly active (> 75% activity). Overall we found little difference in activities from minor changes in stem length (20 cf. 21), or between neighboring targets differing by a single nucleotide in start position. However, there were several exceptions which suggest that all sequences, irrespective of similarities in target site or design, may be useful candidates. We encountered technical limitations with GFP reporter assays when the target domain was long and or when the distance between the target site and fusion junction was large. Assay performance was improved by dividing large targets into several shorter domains.
conclusionIn summary, our novel selection process resulted in a large panel of highly active shRNAs spanning the HIV-1 genome, representing excellent candidates for use in multiple shRNA gene therapies. Our core selection method ensuring maximal conservation in the processed product(s) is also widely applicable to other shRNA applications.
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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.