Partnering with bluebird bio for Better Gene Therapy Tools

by Gina Wadas Viruses are experts at infiltrating the body, as the SARS-CoV-2 virus (and resulting COVID-19 pandemic) have demonstrated. Their efficiency at targeting specific cells makes them useful drug delivery vehicles, known as viral vectors. Viral vectors are modified viruses that transport therapeutic “packages” to diseased cells. These packages contain instructions with modified or designed DNA or RNA to correct or supplement a faulty or missing gene. Though viral vector-based gene therapies are among the most advanced treatments for congenital and acquired diseases, producing them is complex and costly.

To address this challenge, Hai-Quan Mao, INBT associate director and materials science and engineering professor, and his team, collaborated with Nolan Sutherland, senior scientist at bluebird bio, a biotechnology company that develops gene therapies. Sutherland wanted Mao’s help to streamline the transfection process in lentiviral vector production. Lentiviral vectors (LVV) are made from a family of viruses that infect people by reverse transcription of their RNA into DNA in their host cells’ genome. During transfection, a key step in viral vector production, a polymer solution is combined with a DNA plasmid mixture to form transfection particles. The procedure is cumbersome and involves complicated solution blending and strict timed dosing. Mao’s team developed a more effective and shelf-stable formulation of DNA particles in a ready-to-dose form. They also discovered that size-controlled sub-micron particles are most effective in transfecting cells and producing viral vectors. Their findings were validated at bluebird bio using the company’s bioreactor, and they compared the new method with the industry standard. The results showed improved vector production yield, shelf stability, handling stability, and quality control of the transfection process. “This new technology will greatly improve the production quality, consistency, and yield of our therapeutic LVVs,” Sutherland said. The team is scaling up production with goals to transfer the technology to the marketplace. Contributors include Jordan Green, INBT associate researcher and biomedical engineering professor, and Sashank Reddy, INBT affiliate researcher and assistant professor of plastic and reconstructive surgery.