A novel strategy for the next generation raav gene therapy and vaccine vector production

The National Institute of Allergy and Infectious Diseases awarded Neovaxsyn Inc. $300,000 on September 1, 2026, under the Allergy and Infectious Diseases Research program (CFDA 93.855) to develop a novel recombinant adeno-associated virus (rAAV) production system optimized for gene therapy and vaccine applications.

Neovaxsyn will design, generate, and evaluate a baculoviral expression system called OneBacMid that enables rAAV assembly in mammalian cells, aiming to improve both quality and yield of rAAV vectors. The approach addresses limitations in current production methods by combining the high titers achieved through insect cell-based baculovirus systems with the proper post-translational modifications required for mammalian gene expression. The technical validation will use HIV-1 envelope glycoprotein antigens for vaccine development applications.

Neovaxsyn Inc., a minority-owned small disadvantaged business located in Ames, Iowa, is the recipient. Performance occurs in Ames, IA, with a period of performance from September 1, 2026, through August 31, 2028. The award is structured as a Small Business Innovation Research (SBIR) Phase I project grant.

Abstract

Despite the commercial availability of recombinant adeno-associated virus (RAAV) vectors for gene delivery, significant opportunities remain to improve RAAV quality and enhance their success in biomedical applications. A therapeutic viral vector requires rigorous optimization of critical quality attributes (CQAS) and high-titer production to meet dosage requirements for large-animal studies and human clinical trials. In this project, we aim to design, generate, and evaluate a novel RAAV production system optimized for mammalian applications, both in terms of quality and yield. Currently, two major RAAV production methods exist: (1) mammalian HEK293-based suspension cell culture, which relies on CO-transfection with two or three plasmids expressing essential protein factors; and (2) recombinant baculovirus (RBV)- mediated production, where insect SF9 suspension cells express AAV REP-cap and the gene of interest (GOI) separately. While the RBV method achieves high yields, IT often lacks proper post-translational modifications essential for functional gene expression in mammalian systems. In contrast, the HEK293 system produces properly modified RAAV but at insufficient purity and yield for therapeutic applications. To address these limitations, we propose a novel production strategy: the development of onebacmid, a baculoviral system designed to express all necessary factors for RAAV generation. Transducing one-RBV into mammalian cells would enable RAAV assembly in a humanized environment, thereby improving both quality and functionality. Our technical approach will be validated using HIV-1 envelope glycoprotein antigens for vaccine development. If successful, this strategy will significantly advance RAAV-based gene therapy and vaccine delivery by addressing a key bottleneck in next-generation viral vector development.