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Updated: Jul 15, 2025

Engineering and Evolution of Synthetic Adeno-Associated Virus AAV Gene Therapy Vectors via DNA Family Shuffling
Published on: April 2, 2012
Double-Strand Break Repair Pathways Differentially Affect Processing and Transduction by Dual AAV Vectors
Anna C Maurer1,2, Brian Benyamini1, Vinson B Fan1
1Department of Molecular and Cell Biology, University of California, Berkeley, CA, USA.
Inhibiting DNA repair pathways like Homologous Recombination (HR) enhances gene delivery using dual recombinant adeno-associated viral vectors (rAAV). This improves the expression of large transgenes, overcoming rAAV size limitations.
Area of Science:
- Molecular Biology
- Gene Therapy
- Virology
Background:
- Recombinant adeno-associated viral vectors (rAAV) are widely used for gene delivery.
- Current rAAV vectors have limited DNA carrying capacity, restricting therapeutic applications.
- Dual trans-splicing vectors expand payload by concatenating rAAV genomes, but efficiency is variable.
Conclusions:
- Host DNA damage repair pathways, specifically HR, play a critical role in rAAV transduction efficiency.
- Targeting HR factors offers a novel strategy to improve gene payload capacity of rAAV vectors.
- Pharmacological inhibition of HR presents a promising approach for enhancing gene therapy delivery.
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