ArticleJournal of virology2021
Targeting Conserved Sequences Circumvents the Evolution of Resistance in a Viral Gene Drive against Human Cytomegalovirus.
Article in Journal of virology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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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
7 citing papers in PubMed.
- Finding the perfect promoter for Cas9 in homing gene drives using single cell transcriptome data.Nature communications · 2026Article
- PyTEA-O: a Python implementation of Two-Entropies Analysis for protein sequence variation analysis.Bioinformatics (Oxford, England) · 2026Article
- Applying CRISPR Technologies for the Treatment of Human Herpesvirus Infections: A Scoping Review.Pathogens (Basel, Switzerland) · 2025Article
- Applications of CRISPR-Cas-Based Genome Editing Approaches Against Human Cytomegalovirus Infection.Biomedicines · 2025Review
- Cas12f1 gene drives propagate efficiently in herpesviruses and induce minimal resistance.Genome biology · 2024Article
- Review
- Viral gene drive spread during herpes simplex virus 1 infection in mice.Nature communications · 2024Article
Corrections and comments
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Gene drives are genetic systems designed to efficiently spread a modification through a population. They have been designed almost exclusively in eukaryotic species, especially in insects. We recently developed a CRISPR-based gene drive system in herpesviruses that relies on similar mechanisms and could efficiently spread into a population of wild-type viruses. A common consequence of gene drives in insects is the appearance and selection of drive-resistant sequences that are no longer recognized by CRISPR-Cas9. In this study, we analyzed in cell culture experiments the evolution of resistance in a viral gene drive against human cytomegalovirus. We report that after an initial invasion of the wild-type population, a drive-resistant population is positively selected over time and outcompetes gene drive viruses. However, we show that targeting evolutionarily conserved sequences ensures that drive-resistant viruses acquire long-lasting mutations and are durably attenuated. As a consequence, and even though engineered viruses do not stably persist in the viral population, remaining viruses have a replication defect, leading to a long-term reduction of viral levels. This marks an important step toward developing effective gene drives in herpesviruses, especially for therapeutic applications.
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Registered trials
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