[SCAN] Gene therapy viral vectors: how to develop and dose them

SCAN

Title: Gene therapy viral vectors: how to develop and dose them

Speaker: Ana Sofia Coroadinha

Affiliation: Cell Line Development and Molecular Biotechnology Lab

Abstract:

After two decades of clinical trials gene therapy has accumulated several evidences of effectiveness. The recent approvals of a gene therapeutic agent in Europe (Alipogene tiparvovec (Glybera®)), an oncolytic viral therapy in E.U.A. (Talimogene Laherparepvec (IMLYGIC™)) and the very encouraging results obtained with chimeric antigen receptor (CAR)-T cells in cancer has lifted the field.

Viral vectors are very effective delivery systems in gene therapy however their development can be cumbersome. The establishment of cell lines for viral vector production is an intensive and time consuming work. In addition virus titration methods are laborious and often lack accuracy. On the other hand the therapeutic dosing is crucial to achieve efficient treatment.

In our research we are developing novel technologies that will contribute for the progress in viral vector and cell line development. Herein we will present two novel technologies: Single-Step Cloning Screening technology (SSCS), for the fast cell line viral vector development and the ViSensors, for virus titration. The SSCS merges cloning and screening by using (i) split-GFP, a green fluorescent protein separated into 2 fragments which fluoresce upon transcomplementation and (ii) recombinase mediated cassette exchange systems. This technology can now be used to establish retroviral and lentiviral gene therapy vector cell lines. To further expand SSCS approach to other virus and in order to quantify virus we are developing Visensors. The latter are cell based biosensors for label-free virus.