A recent study published in Human Gene Therapy has uncovered that DNA impurities, including plasmid and host cell DNA, are encapsulated as single-stranded DNA within recombinant adeno-associated virus (rAAV) capsids. Led by Kazuhisa Uchida from Kobe University, the research highlights a critical quality control challenge in the production of these widely used gene therapy vectors.

The study analyzed purified rAAV samples and identified DNA impurities originating from three plasmids. Unlike double-stranded DNA, these single-stranded impurities may have distinct effects when used in gene therapy, prompting researchers to call for a reevaluation of their impact.

Dr. Thomas Gallagher, Managing Editor of Human Gene Therapy, emphasized the study’s significance: “Understanding the sources and generation of DNA impurities is vital for improving manufacturing efficiency and ensuring the safety and efficacy of rAAV therapies.”

This research underscores the need for further investigation into single-stranded DNA impurities to enhance the purity and effectiveness of rAAV-based gene therapies. By addressing these challenges, scientists aim to reduce adverse events and improve outcomes for patients.