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Updated: Jun 26, 2025
08:24
CRISPR-Cas9 Genome Editing of Rat Embryos using Adeno-Associated Virus AAV and 2-Cell Embryo Electroporation
Published on: March 15, 2024
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AAV-mediated genome editing is influenced by the formation of R-loops
Francesco Puzzo1,2, Magdalena P Crossley3, Aranyak Goswami1,2
1Department of Genetics, Stanford University, Stanford, CA.
Biorxiv : the Preprint Server for Biology
|May 20, 2024
Summary
Genomic R-loops, structures found in highly transcribed genes, promote the integration of adeno-associated viral vectors (AAV). Modulating R-loops could improve gene therapy safety and predict off-target integration sites.
Area of Science:
- Molecular Biology
- Genetics
- Gene Therapy
Background:
- Recombinant adeno-associated viral vectors (rAAV) are widely used for in vivo gene therapy due to their ability to stimulate homologous recombination (AAV-HR).
- However, rAAV integration into the genome can lead to off-target mutations, posing safety concerns.
Conclusions:
- High levels of R-loops in highly transcribed genes promote rAAV vector genome integration.
- Modulating R-loops may offer a strategy to improve the safety and efficacy of rAAV-mediated genome editing.
- Understanding R-loop dynamics can help predict genomic regions susceptible to rAAV insertional mutagenesis.
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