Silencing Lentiviral Vector Cargo Gene To Aid Cell Therapy Manufacturing

By Sherin Parokkaran Johny, Maria Ababi, Harry Jenkins, Lorna McCall, Keith Meaney, Qian Liu, Maria I Patrício, Matthew Tridgett

Efficient lentiviral vector (LVV) production is essential for advancing cell therapies, yet certain cargo genes can hinder manufacturing by reducing cell viability and limiting yields. A novel gene-silencing approach addresses these challenges by suppressing cargo gene expression during the production window, achieving up to 95% knockdown across multiple promoters. This strategy significantly enhances LVV titres, up to four times higher, while improving producer cell viability and enabling recovery of cell lines previously deemed unrecoverable.

Beyond yield improvements, silencing reduces residual host cell DNA by as much as 86%, minimizing downstream processing burdens and improving overall product quality. The system is versatile, supporting a wide range of cargo genes, including cytotoxic ones, and integrates seamlessly into XOFLX™ producer cell workflows. By mitigating risks and lowering costs, this innovation accelerates the development of LVV-based therapies and expands patient access to advanced treatments. Assimilate how gene silencing can transform lentiviral manufacturing efficiency and reliability.