Peer-Reviewed White Paper

Advanced Analytical Approaches for Accelerated Development of Gene Therapy Products


Jennifer S. Chadwick, PhD
Kirtland Poss, MBA
Shiaw-Lin Wu, PhD


Advanced therapeutic platforms like gene and cell therapies offer tremendous potential for treating unmet medical needs, but have remained extremely challenging to develop successfully, largely because their molecular platforms and clinical delivery systems are highly complex. Obtaining a better understanding of specific structural attributes that influence clinical delivery and outcomes is essential for advancing both individual gene therapy candidates, as well as the emerging vector/gene platforms on which they are based. In particular, identifying and controlling specific molecular attributes of a vector, quantifying vector delivery to the target therapeutic site and correlating therapeutic protein expression in vivo with clinical response are all now beginning to emerge as important underpinnings in leading gene therapy development programs. Concurrently, advances in high-resolution LC-MS based vector characterization, in situ quantification and in vivo expression profiling approaches are increasingly being applied to enable improved program understanding, controls and clinical outcomes. This White Paper describes leading approaches in detailed characterization and quantitation of gene therapy vectors, delivery to target tissues and therapeutic protein expression from development through regulatory package submission. It conveys how understanding the relationship between specific molecular attributes identified through high-resolution analyses and quantification of related in vivo expression influences efficacy, and can guide, de-risk and improve development of complex gene therapy products. The primary focus is on AAV systems with inclusion of related aspects of LVV, however the methods reviewed may be applied to other related platforms for advanced therapeutic medicinal products as well.

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