William Connors is scientist, research-upstream processing at Biopharma Production, Avantor.

William Connors

Adeno-associated virus (AAV) has emerged as a leading platform for gene delivery for treating various diseases due to its excellent safety profile and efficient transduction to various target tissues. However, the large-scale production and long-term storage of viral vectors are not efficient, resulting in lower yields, moderate purity, and shorter shelf-life compared to recombinant protein therapeutics. The manufacturing of AAV includes several upstream, downstream, and fill/finish unit operations. Cell lysis is one of the key downstream unit operations, where the outer boundary or cell membrane is broken down or destroyed to release viral vector from the host cell. During cell lysis and separation of viral vector from cell debris, viral vectors are exposed to harsh shear stress that aggregates, unfolds, and precipitates virus. In this paper, the authors discuss a novel cell lysis solution that is efficient and generates low foam, making it easy to use. The novel solution also protects the viral vector from shear-induced damage during the manufacturing process, resulting in an improved viral vector titer. The solution is environmentally friendly and biodegradable.

Submitted: March 18, 2022
Accepted: March 31, 2022

Arvind Srivastava*, arvind.srivastava@avantorsciences.com, is technical fellow, research & development; Courtney O’Dell is senior scientist; Lori Fortin is senior research manager; Jonathan Fura is manager, research & development; William Connors is scientist, research-upstream processing; and Nandkumar Deorkar is vice-president, research & development; all are at Biopharma Production, Avantor. Michael Hill was formerly senior research scientist at Avantor.

*To whom all correspondence should be addressed.

When referring to this article, please cite it as A. Srivastava et al., “A Novel Cell Lysis Method to Improve the Viral Vector Manufacturing Process,” 

Articles

Researchers demonstrated a new cell lysis method using a novel solution to improve viral vector production.