Large scale lentiviral vector production

Lentiviral vectors (LV) are remarkable in their ability to insert their genetic payload into a target cell's genome. This affects a permanent genetic change in the target which is propagated through to its progeny. While there are several means of genetic modification, few are capable of permanent modification of target cells. Amongst all vectors for gene delivery, LV are unique in unparalleled efficiency, safety, lack of toxicity and ability to modify non-dividing target cells. They have therefore come to be recognised as a key reagent required for the efficient development of the burgeoning cell therapy, as well as gene therapy industries. However, although LV represent a well understood and robust technology, there is no manufacturing methodology for very large-scale LV production. This is now an acknowledged bottle-neck both for clinical trials and for commercial exploitation of many cell and gene therapy products in current development. We propose to address this unmet need

* Lentiviral vectors (LV) are used to genetically modify target cells. The main commercial application of LVs is in vitro production of cellular therapeutics, although they can be used as therapeutic agents in their own right and for generation of protein producer cells. While small-scale production is well established, a process for very large-scale production has not been developed. Recently, commercial demand for LV has increased greatly. Large-scale production is a major unmet need and its lack a bottleneck esp. in the marketing of cellular therapies. The challenge of large-scale LV production is multifaceted, requiring a deep understanding of lentiviral biology, as well as skilful genetic and cellular engineering, appreciation of regulatory / GMP considerations, industrial/pharmaceutical scale production issues as well as an understanding of the down-stream clinical applications.

As described in proposal submitted to IUK