(421a) Food, Pharmaceutical and Bioengineering Division Award in Chemical Engineering: Directed Evolution of New Viruses for Therapeutic Gene Delivery
AIChE Annual Meeting
2017
2017 Annual Meeting
Food, Pharmaceutical & Bioengineering Division
Division Plenary: Food, Pharmaceutical, and Bioengineering Division (Invited Talks)
Tuesday, October 31, 2017 - 3:25pm to 4:05pm
As an alternative approach, we were the first to develop and have since been implementing directed evolution â involving the iterative genetic diversification of a viral genome and functional selection for desired properties â to address a number of problems with AAV. Genetic diversification has included the random diversification of peptide sequences at defined locations in the capsid, random point mutagenesis of the cap gene, and recombination of cap genes from a number of parental serotypes to create random chimeras. Using a range of in vitro and in vivo strategies to select the resulting large (~108) libraries for improved function, we have evolved AAVs for evasion of neutralizing antibodies, enhanced biodistribution and spread within a target tissue, greatly improved delivery efficiency, and targeted delivery in vitro and in vivo, thereby substantially improving the vectorsâ capacity to meet human therapeutic needs.