Significant Improvements In Total Lentiviral Titer And Quality Seen By Implementing Process C, A Perfusion-Based System

By Carol Knevelman, Vice President, Head of Process Research & Development, Oxford Biomedica

The advanced therapy space has reached an inflection point – with increasing focus on the novel biotherapeutics that may represent the next frontier of treatment for many rare and intractable diseases, developers are continuing to innovate on the production processes that will enable the safe, efficient, and cost-effective production of these drugs. Viral vectors are one of the most proven and efficient vehicles for gene transfer, facilitating the targeted modification of specific cell types or tissues for the treatment of genetic diseases.

There are several types of viral vectors commonly used in advanced therapy applications today, including lentiviral vectors, which offer a number of advantages as gene transfer tools owing to their ability to transduce both dividing and nondividing cells, efficiently integrate into the host genome, carry large transgenes or multiple genes, and allow for stable, long-term transgene expression. As with many viral vectors utilized in cell and gene therapies, lentiviral manufacture is predominantly achieved following transient transfection of immortalized human cells with plasmid DNA encoding viral components. Whilst this approach enables significant flexibility with vector design and development, production by means of transient transfection presents a number of challenges for manufacturing at larger scales.