Optimizing Lentiviral Vector Development For In Vivo Delivery Of Cell And Gene Therapies

By Vijetha Bhat, CGT Technical Expert; Wenling Dong, Head of Upstream Process Development; and F. Michael Haller, Ph.D., Associate Director, R&D Downstream Science

Lentiviral vectors remain central to ex vivo gene modification, while growing interest in in vivo CAR-T therapies and gene editing is driving increased demand for reliable manufacturing solutions. Yet several technical challenges continue to complicate production and purification. Infectivity assays can take days to deliver results, limiting opportunities for real-time process monitoring and timely adjustments. Large impurities may closely resemble the vector, making effective separation difficult.

Unlike established approaches used in adeno-associated virus (AAV) workflows, lentiviral downstream processing lacks an established method for separating full particles from empty ones. The vector's sensitivity to process conditions, including shear and pH, further constrains purification options and the ability to maintain product quality. These challenges become even more significant for in vivo applications, where purity requirements are more demanding.

Originally published in Biocompare, this article examines why these manufacturing and analytical gaps persist and considers where contract development and manufacturing organizations (CDMOs) can support developers without in-house capabilities. Read the article to explore emerging analytical and purification approaches for addressing these challenges.