Unpacking the challenges of AAV gene therapy: exploring capsid engineering, immunogenicity management, and scalable manufacturing solutions

"Although it has been over 50 years since AAV was first described as a possible vector...we still lack a comprehensive understanding of its biology and mechanism of action.” Abi Pinchbeck (Editor, BioInsights) speaks to Sherif Gabriel (CEO and Co-Founder primAAVera Therapeutics) about the persistent challenges facing AAV-based gene therapies, including tissue-specific targeting, immune responses at high vector doses, and the lack of standardized manufacturing protocols. They explore how progress in capsid engineering, producer cell line development, and human-relevant selection platforms could enhance specificity, reduce immunogenicity, and support scalable clinical translation. Sherif also emphasizes the importance of early-stage design for manufacturability, offers practical guidance for early-stage vector developers, and reflects on the potential of emerging platforms such as Bocaparvovirus.