ArticleAntiviral research2016
Detection of treatment-resistant infectious HIV after genome-directed antiviral endonuclease therapy.
Article in Antiviral research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
27 citing papers in PubMed, 43 citations in OpenAlex.
- High-resolution Inference of Multiplexed Anti-HIV Gene Editing using Single-Cell Targeted DNA Sequencing.bioRxiv : the preprint server for biology · 2024Article
- Precise excision of HTLV-1 provirus with a designer-recombinase.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Review
- CRISPR-Cas9 gene editing of hepatitis B virus in chronically infected humanized mice.Molecular therapy. Methods & clinical development · 2021Article
- Gene Transfer in Adeno-Associated Virus Seropositive Rhesus Macaques Following Rapamycin Treatment and Subcutaneous Delivery of AAV6, but Not Retargeted AAV6 Vectors.Human gene therapy · 2021Article
- MultiplexedViruses · 2020Article
- Humanized Mouse Model of HIV-1 Latency with Enrichment of Latent Virus in PD-1Journal of virology · 2019Article
- Genome editing for the treatment of tumorigenic viral infections and virus-related carcinomas.Frontiers of medicine · 2018Review
- Viral diversity is an obligate consideration in CRISPR/Cas9 designs for targeting the HIV reservoir.BMC biology · 2018Article
- CRISPR/Cas9 and Genome Editing for Viral Disease-Is Resistance Futile?ACS infectious diseases · 2018Review
- CRISPR/Cas9 system targeting regulatory genes of HIV-1 inhibits viral replication in infected T-cell cultures.Scientific reports · 2018Article
- CRISPR/Cas9 Genome Editing to Disable the Latent HIV-1 Provirus.Frontiers in microbiology · 2018Review
- The therapeutic landscape of HIV-1 via genome editing.AIDS research and therapy · 2017Review
- Tuning DNA binding affinity and cleavage specificity of an engineered gene-targeting nuclease via surface display, flow cytometry and cellular analyses.Protein engineering, design & selection : PEDS · 2017Article
- Novel AIDS therapies based on gene editing.Cellular and molecular life sciences : CMLS · 2017Review
- Excision of Latent HIV-1 from Infected Cells In Vivo: An Important Step Forward.Molecular therapy : the journal of the American Society of Gene Therapy · 2017Article
- In vivo dynamics of AAV-mediated gene delivery to sensory neurons of the trigeminal ganglia.Scientific reports · 2017Article
- Gene Editing Approaches against Viral Infections and Strategy to Prevent Occurrence of Viral Escape.PLoS pathogens · 2016Review
- Disruption or Excision of Provirus as an Approach to HIV Cure.AIDS patient care and STDs · 2016Article
- In vivo disruption of latent HSV by designer endonuclease therapy.JCI insight · 2016Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
Incurable chronic viral infections are a major cause of morbidity and mortality worldwide. One potential approach to cure persistent viral infections is via the use of targeted endonucleases. Nevertheless, a potential concern for endonuclease-based antiviral therapies is the emergence of treatment resistance. Here we detect for the first time an endonuclease-resistant infectious virus that is found with high frequency after antiviral endonuclease therapy. While testing the activity of HIV pol-specific zinc finger nucleases (ZFNs) alone or in combination with three prime repair exonuclease 2 (Trex2), we identified a treatment-resistant and infectious mutant virus that was derived from a ZFN-mediated disruption of reverse transcriptase (RT). Although gene disruption of HIV protease, RT and integrase could inhibit viral replication, a chance single amino acid insertion within the thumb domain of RT produced a virus that could actively replicate. The endonuclease-resistant virus could replicate in primary CD4(+) T cells, but remained susceptible to treatment with antiretroviral RT inhibitors. When secondary ZFN-derived mutations were introduced into the mutant virus's RT or integrase domains, replication could be abolished. Our observations suggest that caution should be exercised during endonuclease-based antiviral therapies; however, combination endonuclease therapies may prevent the emergence of resistance.
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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.