ArticleNature biotechnology2025
Genome engineering with Cas9 and AAV repair templates generates frequent concatemeric insertions of viral vectors.
Article in Nature biotechnology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed.
- Syncytium-forming HSV-1 in cancer gene therapy: From molecular mechanisms to clinical translation.Virulence · 2026Review
- Genetically engineered hypoimmunogenic iPSCs: Strategies and considerations for clinical applications.Regenerative therapy · 2026Review
- Unlocking the curative potential of gene transfer and editing for hematopoietic disorders.Experimental hematology · 2026Review
- Double-stranded DNA donors and CRISPR-Cas9 for universal correction of mutations causing cystic fibrosis in human airway cells.Molecular therapy. Nucleic acids · 2026Article
- Functional editing of the OTC locus by targeted integration with phenotype correction and restoration of endogenous expression patterns.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Gene editing of hematopoietic stem cells: applications and advances.International journal of hematology · 2026Review
- Strategies and mechanisms of precision genome engineering: From gene editing to genome writing.iMetaOmics · 2026Review
- A PepFect14 analog improves non-viral CRISPR delivery in primary human cells to facilitate genome editing and repair.Bioengineering & translational medicine · 2026Article
- RNA delivery to the corneal endothelium using charge-altering releasable transporters.Science advances · 2026Article
- Next-generation programmable cell therapies for precision medicine.Nature reviews. Genetics · 2026Review
- Selection of human hematopoietic stem cells bearing the intended functional edit by transient AND-gate reporters.Nature biotechnology · 2026Article
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
- Efficient multi-kilobase knock-ins in mice and cell lines using CRISPR/Cas9 and rAAV donors with unbiased whole-genome characterization by LOCK-seq.Nucleic acids research · 2026Article
- Enhancement of therapeutic transgene insertion for treatment of murine phenylketonuria.Molecular therapy. Nucleic acids · 2026Article
- DNMT3A R882H Is Not Required for Disease Maintenance in Primary Human AML but Is Associated with Increased Leukemia Stem Cell Frequency.Cancer discovery · 2026Article
- Review
- A precision gene-engineered B cell medicine producing sustained levels of active factor IX for hemophilia B therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- CRISPR-based therapeutic genome editing for inherited blood disorders.Nature reviews. Drug discovery · 2025Review
- AAV capsid prioritization in normal and steatotic human livers maintained by machine perfusion.Nature biotechnology · 2025Article
- The editable landscape of the yeast genome reveals hotspots of structural variant formation.Science advances · 2025Article
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16 authors.
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Abstract
CRISPR-Cas9 paired with adeno-associated virus serotype 6 (AAV6) is among the most efficient tools for producing targeted gene knockins. Here, we report that this system can lead to frequent concatemeric insertions of the viral vector genome at the target site that are difficult to detect. Such errors can cause adverse and unreliable phenotypes that are antithetical to the goal of precision genome engineering. The concatemeric knockins occurred regardless of locus, vector concentration, cell line or cell type, including human pluripotent and hematopoietic stem cells. Although these highly abundant errors were found in more than half of the edited cells, they could not be readily detected by common analytical methods. We describe strategies to detect and thoroughly characterize the concatemeric viral vector insertions, and we highlight analytical pitfalls that mask their prevalence. We then describe strategies to prevent the concatemeric inserts by cutting the vector genome after transduction. This approach is compatible with established gene editing pipelines, enabling robust genetic knockins that are safer, more reliable and more reproducible.
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