Generation of novel AAV serotype with enhanced infectivity, specificity, and lower toxicity via π-Icosa AAV Capsid engineering platform
Adeno-associated virus (AAV) is commonly used in gene therapy research but has limitations for targeted gene therapy. In vivo gene delivery faces challenges like ineffective uptake, off-target infections, and neutralization by pre-existing antibodies. AAV capsid engineering is a promising solution to overcome these challenges.
PackGene’s π-Icosa system is an advanced AAV capsid engineering platform that constructs and screens capsid libraries to identify top variants with enhanced infectivity and reduced off-target effects. The process involves generating a diverse capsid gene library using deep mutation and rational design, with the assistance of an AI-based prediction model, followed by in vivo testing to verify biodistribution and tissue tropism. This data guides subsequent library design and testing to identify the most efficient AAV variant.
The π-Icosa system has successfully engineered AAV variants with improved specificity in the central nervous system (CNS), muscle, and other tissues. A novel serotype, AAV-PG008, was created by inserting random peptides into the AAV9 capsid, resulting in better CNS targeting compared to known serotypes. Another variant, AAV-PG007, was generated through a combination of rational design and directed evolution, showing increased muscle targeting and reduced off-target effects in mice and monkeys. Another set of AAV6 variants generated by π-Icosa system show 10 times higher infection efficiency to primary human T-cells than the wildtype.
PackGene’s π-Icosa AAV Capsid Engineering Platform provides a reliable solution to the generation of novel AAV capsid with improved infectivity, specificity, and reduced toxicity, enabling the development of more precise and effective gene therapies.