Optimizing vector design for improved quality and safety
Optimizing the safety of lentiviral vectors has been one of the main focal points of lentiviral vector development. Likewise, the design of the lentiviral backbone and the therapeutic payload cassette can influence the manufacturability of the particles, for example their quality and potency features. Optimizing those features will further improve the safety and efficacy profile of future ex vivo and in vivo gene therapies.
To date the safety of over 25 lentivirus backbones has been tested in more than 200 clinical trials. SIRION Biotech will discuss the main features of those backbones and the main strategies to further optimize their safety. We will also give insights into datasets from our viral vector know-how hub to illustrate how payload design strategies can affect the manufacturability of the lentiviral particles and their usage to develop ex vivo and in vivo gene therapies. Our viral vector know-how hub includes data derived from over 6,000 lentiviral vectors. Examples of data modalities are payload sequence composition, as well as their associated manufacturing metrics, such as productivity, batch titers, and specific types of product-related impurities.
Transmembrane proteins with CARs and TCRs constructs, as examples of ex vivo gene therapy components, form a highly relevant payload dataset from our vector know-how hub. We will discuss particular aspects of the manufacturing process for these types of components, including payload translation and their inclusion into the cell host membrane as a root cause of low productivity and product-related impurities. This suboptimal quality, in turn, can ultimately decrease the cell transduction efficiency during the manufacturing process of CAR-T cells. We will also present a complementary strategy to optimize cell transduction by using LentiBOOST®, a chemical transduction enhancer, as part of developing a cGMP-compliant process to manufacture CD19-CAR T cells.
Join SIRION BIOTECH’s Dr Michael Salomon and Dr Irene Ferreira as they discuss strategies to develop lentiviral lead vectors for ex vivo and in vivo gene therapy that aim to optimize the manufacturability of the particles as well as their safety and efficacy profile.
Key Learning Objectives
- The main features of lentiviral backbones in clinical development and the main strategies to further optimize their safety.
- The impact of the therapeutic payload cassette design on the manufacturability of the lentiviral particles, including their quality and safety features.
- Strategies to improve cell transduction efficiency during the manufacturing process of an ex vivo gene therapy.
– Dr. Michael Salomon, SVP Development
– Dr. Irene Ferreira, Head of Clinical Support, Cell & Gene Therapy
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