Session Chairs: Rob McCombie, Avidity Biosciences, Raj Poudel, Mammoth Biosciences, Inc., and Zenobia Taraporewala, BioMarin Pharmaceutical Inc.

The first wave of cell and gene therapies (CGT) developed, mostly, with viral vectors such as adeno-associated virus (AAV), adenovirus, lentivirus and retrovirus were transformative in treating many intractable diseases.  Yet, the widespread adoption of these novel therapies has been limited by the challenges associated with viral delivery systems. Notably, challenges due to limited packaging capacity, safety concerns with administration of high doses and genotoxicity, efficacy concerns with inability to redose due to seroconversion, manufacturing complexities requiring product-specific optimizations, copurifying impurities impacting safety and potency, and high production costs limiting scalability and clinical application.

Non-viral delivery methods, initially developed for the delivery of plasmid DNA, are being adopted for in vivo or ex vivo delivery of RNA and genome editing (GE) components using bespoke lipid nanoparticles (LNPs) and physical delivery methods like electroporation and sonoporation. As a result, the scope of treatable conditions with CGT products has greatly expanded with non-viral delivery approaches that are being tailored to target hepatic and extrahepatic sites such as lung. By overcoming the limitations of viral delivery, non-viral methods are poised to drive the development of the “NextGen” CGTs.  

This session will examine the challenges and discuss the potential solutions encountered during CMC development of in vivo and ex vivo non-viral mediated CGTs.

Session Speaker:

Lipid Nanoparticles-Points to Consider For Non-Viral Delivery of RNA-based Therapeutics

Mo Heidaran, Cellx Consulting

INS1203: RNA-End Joining Technology Enables A Dual AAV Approach for ABCA4 Gene Replacement in Stargardt Disease

Kathryn Hilde, Insmed Incorporated

CRISPR Genome Editing Components Used for Ex-Vivo Genome-Editing of Allogeneic Cell Therapy Products: Their Clearance and Their Effects

Alex Chialastri, Century Therapeutics

Additional Panelist:

Kathleen Francissen, Genentech, a Member of the Roche Group

Raj Poudel

Appearances