Biomanufacturing: Cell and Gene Therapy with a case study on LVV Manufacturing with Producer cell line

Viral vectors have revolutionized gene delivery for cell and gene therapy over the past two decades. Adeno-associated viruses (AAVs) are widely utilized for in vivo gene replacement and editing, while lentiviral and retroviral vectors (LVVs and RVVs) offer sustained gene expression for cell therapy applications. Despite their efficacy, challenges persist in efficient vector manufacturing, driven by diverse serotypes, capsid variants, and transient transfection methods. Developing a robust and scalable manufacturing process is time-consuming and costly.

To address these challenges, collaboration with a Contract Development and Manufacturing Organization (CDMO) during the early stages of clinical programs proves beneficial. Genezen, as a leading CDMO, has implemented Tet-off Producer Cell Line (PCL) systems and platform processes to overcome traditional production limitations. For LVVs, our approach consistently achieves high titers exceeding 6e6 IU/mL across multiple productions, demonstrating superior performance compared to traditional methods. The Tet-off PCL system offers enhanced downstream processing, superior residual profiles, and the ability to generate high-titer super lots.

By eliminating the need for cGMP-grade plasmids, our approach significantly reduces costs and enhances commercial scalability, promising consistent batch yields. This innovation represents a significant advancement in gene and cell therapy manufacturing, potentially improving patient access to therapies based on lentiviral vectors.

Pratima Cherukuri, with over 15 years of expertise in viral vector process development, analytics, and production, currently serves as the Chief Scientific Officer (CSO) at Genezen, a leading gene and cell therapy Contract Development and Manufacturing Organization (CDMO). Joining Genezen in 2019, she has played a pivotal role in shaping the company's scientific direction. Prior to her role at Genezen, she held a key position at Covance Laboratories, where she led Bioassay development and validation activities. During her tenure at the Indiana University Vector Production Facility, she spearheaded the development of next-generation viral vector processes for Lentiviral and Retroviral vectors. Her responsibilities extended to analytical development and overseeing the delivery of over 15 GMP batches. Pratima has been instrumental in the design of Genezen labs and GMP suites. In her current role, she leads the development of scalable, robust, and economically viable viral vector production processes. Additionally, as the technical sales lead, she collaborates with Genezen commercial teams and clients to ensure scientific and operational excellence, showcasing her commitment to advancing gene and cell therapy technologies. She has a double master's in biotechnology and is a Cytogenetics major and holds an MBA from Kelley School of Business.