SCAN:Re-designing virus and cells for the development of complex biopharmaceuticals: vaccines and gene therapy vectors

ITQB Scan Seminar

Title: Re-designing virus and cells for the development of complex biopharmaceuticals: vaccines and gene therapy vectors

Speaker: Ana S. Coroadinha

From: Cell Line Development and Molecular Biotechnology Lab @ Animal Cell Unit

Abstract:

The increasing demand of pharmaceutical bioproducts has placed significant pressure to develop high-yielding and dynamic mammalian cell-based production systems. Additionally, stringent quality standards are required for bioproducts used in human therapies. Virus based biopharmaceuticals (VBBs) represent one of the most promising biopharmaceuticals of the 21st century medicine, covering many successful prophylactic, therapeutic and clinical applications such as vaccination, cancer treatment and gene therapy. From the manufacturing perspective, virus based biopharmaceuticals development and production is highly challenging due to their inherent complexity requiring apt cell lines and optimized culture conditions.
Re-designing the recombinant virus or the host cell line can significantly enhance the production and quality of the therapeutic viral product and latter its efficacy in clinic.
From the molecular biology perspective the virus must be decomposed to a therapeutic format where the number of viral components is minimized in order to increase its safety and reduce its complexity for production. On the other hand the cell must provide a metabolic suited machinery and environment. Using functional genomics tools, more specifically transcriptional and metabolic profiling it was possible to unveil bottlenecks in the manufacturing of retrovirus based biopharmaceuticals. For example, retrovirus production activates several lipid biosynthetic, amino acid and nucleic acid pathways. The results obtained could not only, unveil metabolic constraints that modulate the virus quality, but also to design strategies to overcome them. A novel high-throughput screening method was implemented allowing to analyze the impact of gene manipulation and cell engineering on virus production.
Challenges and novel strategies applied on the development of virus based biopharmaceuticals will be presented and discussed.