ArticleRetrovirology2010
Anticipating and blocking HIV-1 escape by second generation antiviral shRNAs.
Article in Retrovirology, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Comprehensive analysis of drugs to treat SARS‑CoV‑2 infection: Mechanistic insights into current COVID‑19 therapies (Review).International journal of molecular medicine · 2020Review
- Novel RNA Duplex Locks HIV-1 in a Latent State via Chromatin-mediated Transcriptional Silencing.Molecular therapy. Nucleic acids · 2015Article
- Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus.World journal of virology · 2015Review
- The impact of HIV-1 genetic diversity on the efficacy of a combinatorial RNAi-based gene therapy.Gene therapy · 2015Article
- Combination siRNA therapy against feline coronavirus can delay the emergence of antiviral resistance in vitro.Veterinary microbiology · 2015Article
- 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
- Unmasking the information encoded as structural motifs of viral RNA genomes: a potential antiviral target.Reviews in medical virology · 2013Review
- Functional in vivo delivery of multiplexed anti-HIV-1 siRNAs via a chemically synthesized aptamer with a sticky bridge.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Therapeutic potential of aptamer-siRNA conjugates for treatment of HIV-1.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2012Review
- Creating genetic resistance to HIV.Current opinion in immunology · 2012Review
- RNAi in the regulation of mammalian viral infections.BMC biology · 2012Article
- 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
- Deep sequencing of virus-infected cells reveals HIV-encoded small RNAs.Nucleic acids research · 2012Article
- Directed HIV-1 evolution of protease inhibitor resistance by second-generation short hairpin RNAs.Antimicrobial agents and chemotherapy · 2012Article
- Antiviral RNAi: translating science towards therapeutic success.Pharmaceutical research · 2011Review
- New approaches to the inhibition of replication of viral pathogens.Expert review of anti-infective therapy · 2011Article
- Inhibition of Hazara nairovirus replication by small interfering RNAs and their combination with ribavirin.Virology journal · 2011Article
- A comparison of multiple shRNA expression methods for combinatorial RNAi.Genetic vaccines and therapy · 2011Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRNA interference (RNAi) is an evolutionary conserved gene silencing mechanism that mediates the sequence-specific breakdown of target mRNAs. RNAi can be used to inhibit HIV-1 replication by targeting the viral RNA genome. However, the error-prone replication machinery of HIV-1 can generate RNAi-resistant variants with specific mutations in the target sequence. For durable inhibition of HIV-1 replication the emergence of such escape viruses must be controlled. Here we present a strategy that anticipates HIV-1 escape by designing 2nd generation short hairpin RNAs (shRNAs) that form a complete match with the viral escape sequences.
resultsTo block the two favorite viral escape routes observed when the HIV-1 integrase gene sequence is targeted, the original shRNA inhibitor was combined with two 2nd generation shRNAs in a single lentiviral expression vector. We demonstrate in long-term viral challenge experiments that the two dominant viral escape routes were effectively blocked. Eventually, virus breakthrough did however occur, but HIV-1 evolution was skewed and forced to use new escape routes.
conclusionThese results demonstrate the power of the 2nd generation RNAi concept. Popular viral escape routes are blocked by the 2nd generation RNAi strategy. As a consequence viral evolution was skewed leading to new escape routes. These results are of importance for a deeper understanding of HIV-1 evolution under RNAi pressure.
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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.