Gene Therapy Vector Production

Virus

This is the workflow for the production of the virus vector, carrying the gene of interest (GOI), which will be used to infect the patient's cells e.g. a target tissue, such as the eye, or the patient's T cells in CAR-T.

Currently, for companies in the early stages of gene therapy, most vector production is still done by transient transfection.

However, for clinical trials, much larger amounts of material will be required. This will not only be very costly using current approaches, there will also be more requirements around batch-to-batch consistency, higher titres needed, and improved vector quality and safety for GMP.

Hence there is an increasing need by gene therapy companies for stable producer cell lines.

Gene Therapy Workflow AAV

Gene Therapy Workflow LV

Given that these cell lines will also be producing a therapeutic/biologic, there is also an implied requirement that these cells lines must be shown to be clonal for regulatory approval by the FDA or other.

Using the tools developed by Solentim for cell line development, some of our first gene therapy customers have already developed and banked stable high producing clones with demonstrated monoclonality in <3 months.

Most customers work with two primary methods of viral gene delivery: Lentivirus (LV) or Adeno-Associated Virus (AAV).

The packaging cells line will produce the capsid or empty virus particle. This is effectively the “mother” cell line for future producer cell lines. They are generally used for making smaller amounts of material by transient transfection.

The producer cell line is a stable cell line for the GOI and is used to manufacture the final clinical materials.

The producer cells will be able to infect isolated patient cells (ex-vivo) e.g. T cells, or have the possibility to be directly injected into patients allowing for long term in-vivo vector production.

Next Steps