ArticleProceedings of the National Academy of Sciences of the United States of America2015
Specific induction of endogenous viral restriction factors using CRISPR/Cas-derived transcriptional activators.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 papers, 1 of them a synthesis that pooled it.
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Who cites it
38 citing papers in PubMed, 1 synthesis or guideline pooled it, 60 citations in OpenAlex.
- Multiple Inhibitory Factors Act in the Late Phase of HIV-1 Replication: a Systematic Review of the Literature.Microbiology and molecular biology reviews : MMBR · 2018Pooled it
- CRISPR/Cas9-Based Genome Editing: Understanding Differences in DNA Repair Pathways, Profiles, and Outcomes.International journal of molecular sciences · 2026Review
- Broad-acting antivirals: the pursuit of pan-viral therapeutics in the era of pandemics.Journal of virology · 2026Review
- Advancements in CRISPR-Cas Systems for Genome Editing towards Eradication of Human Microbial Pathogens.Molecular biotechnology · 2026Review
- Recent Advances in Nanoparticle-Based Antiretroviral Drug Delivery Systems for HIV Treatment and Prevention: A Comprehensive Review.International journal of nanomedicine · 2025Review
- Precision in Action: The Role of Clustered Regularly Interspaced Short Palindromic Repeats/Cas in Gene Therapies.Vaccines · 2024Review
- Current Approaches to Epigenetic Therapy.Epigenomes · 2023Review
- Transient and tunable CRISPRa regulation of APOBEC/AID genes for targeting hepatitis B virus.Molecular therapy. Nucleic acids · 2023Article
- A CRISPR-Cas Cure for HIV/AIDS.International journal of molecular sciences · 2023Review
- Computational analysis of cas proteins unlocks new potential in HIV-1 targeted gene therapy.Frontiers in genome editing · 2023Article
- Strategies for HIV-1 suppression through key genes and cell therapy.Frontiers in medicine · 2023Review
- Therapeutic Applications of the CRISPR-Cas System.Bioengineering (Basel, Switzerland) · 2022Review
- Application of CRISPR-Cas9 Gene Editing for HIV Host Factor Discovery and Validation.Pathogens (Basel, Switzerland) · 2022Review
- HIV cure strategies: which ones are appropriate for Africa?Cellular and molecular life sciences : CMLS · 2022Review
- Updates on CRISPR-based gene editing in HIV-1/AIDS therapy.Virologica Sinica · 2022Review
- Application of CRISPR/Cas Genomic Editing Tools for HIV Therapy: Toward Precise Modifications and Multilevel Protection.Frontiers in cellular and infection microbiology · 2022Review
- Review
- CRISPR/Cas technology as a promising weapon to combat viral infections.BioEssays : news and reviews in molecular, cellular and developmental biology · 2021Review
- CRISPR-Cas9: A Preclinical and Clinical Perspective for the Treatment of Human Diseases.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Review
- CRISPR Technology in Gene-Editing-Based Detection and Treatment of SARS-CoV-2.Frontiers in molecular biosciences · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
Whereas several mammalian proteins can restrict the replication of HIV-1 and other viruses, these are often not expressed in relevant target cells. A potential method to inhibit viral replication might therefore be to use synthetic transcription factors to induce restriction factor expression. In particular, mutants of the RNA-guided DNA binding protein Cas9 that have lost their DNA cleavage activity could be used to recruit transcription activation domains to specific promoters. However, initial experiments revealed only weak activation unless multiple promoter-specific single guide RNAs (sgRNAs) were used. Recently, the recruitment of multiple transcription activation domains by a single sgRNA, modified to contain MS2-derived stem loops that recruit fusion proteins consisting of the MS2 coat protein linked to transcription activation domains, was reported to induce otherwise silent cellular genes. Here, we demonstrate that such "synergistic activation mediators" can induce the expression of two restriction factors, APOBEC3G (A3G) and APOBEC3B (A3B), in human cells that normally lack these proteins. We observed modest activation of endogenous A3G or A3B expression using single sgRNAs but high expression when two sgRNAs were used. Whereas the induced A3G and A3B proteins both blocked infection by an HIV-1 variant lacking a functional vif gene by inducing extensive dC-to-dU editing, only the induced A3B protein inhibited wild-type HIV-1. These data demonstrate that Cas9-derived transcriptional activators have the potential to be used for screens for endogenous genes that affect virus replication and raise the possibility that synthetic transcription factors might prove clinically useful if efficient delivery mechanisms could be developed.
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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.