Applying Next Generation Sequencing (NGS) To Accelerate Cell And Gene Therapy Product Development

By Pamela Hamill, Bradley Hasson, Rebecca Bova, Leyla Diaz, and Alison Armstrong

The burgeoning field of gene therapy is witnessing a transformative shift with the integration of Next Generation Sequencing (NGS) technologies, particularly in the development of viral vector-mediated therapies such as adeno-associated virus (AAV) and lentivirus. This comprehensive overview emphasizes how NGS not only accelerates product development but also enhances the characterization of therapeutic materials, thereby addressing urgent medical needs.

NGS mitigates risks associated with sequence variants that traditional methods may overlook. Regulatory bodies like the EMA and FDA increasingly endorse NGS for its ability to ensure viral safety and confirm vector identity, especially in complex regions like inverted terminal repeats (ITRs). Furthermore, the case study highlighted demonstrates the effectiveness of hybrid sequencing approaches, combining short-read and long-read technologies. It aims to achieve over 99% mapping accuracy to AAV-associated genes while effectively identifying encapsidated DNA impurities.

The potential of NGS extends to safety testing for lentiviral therapies, where it plays a crucial role in integration site analysis to evaluate genotoxicity risks. As FDA guidelines evolve to include whole genome sequencing for human allogeneic cell therapies it is imperative that thorough safety assessments become clear. NGS stands as a pivotal tool in the quest for safe and effective gene and cell therapies, promising to redefine the landscape of medical treatments. Access the content to learn more.