QC Pipeline Development

Interest in the use of rAAVs for clinical applications is steadily increasing, yet quality control measures for assessing genome integrity for manufactured clinical vectors have changed very little. The recent use of high-throughput sequencing approaches has revealed the prevalence of incomplete/truncated genomes in packaged rAAV particles.  Although it can be argued that compromised transgenes are functionally inert, a high percentage of incompletely packaged genomes may impact the required dosages needed to treat patients. This may also raise the cost of production for efficacious amounts of therapeutic virus.  We are developing pipelines based on a method we have pioneered to profile vector preparations on a high-throughput scale with single-particle resolution called Adeno-Associated Virus Genome Population sequencing (AAV-GPseq). This platform will allow investigators to precisely assess the quality of manufactured rAAVs and will help determine whether certain vector designs will be safe for clinical use.