Bioprocess Development and Bioreactor Scale-Up for the Production of Recombinant Lentiviral Viral Vectors in HEK293 Suspension Cell Culture

Abstract

Therapeutic applications of viral vectors that initially targeted rare monogenic diseases have now grown to a broader set of indications including cell and gene therapy applications and vaccines. This has prompted the need to increase biomanufacturing capacities, which will require adjustments in the biomanufacturing space to increase yield and lower cost of goods of large-scale productions. HEK293 cells have been widely used for the production of viral vectors because they can grow rapidly in suspension and allow for different modes of production: batch, fed-batch and perfusion. Here we review methods and platforms for producing lentiviral vectors in HEK293 cells grown in serum-free media and the principles and challenges of optimizing and scaling up of bioprocesses in various bioreactors. Lentiviral vectors are particularly difficult to manufacture due to their labile nature. These challenges will be considered in view of current processes and future trends emerging to resolve bottlenecks and existing limitations.