报告题目：Innovation by Evolution: Engineering Next-Generation of Adeno-Associated Viral Vectors for Gene Therapeutics in Central Nervous System
Gene therapy, the delivery of genetic material to the cells of a patient for therapeutic benefit, has been increasingly successful over the past decade. The most successful gene delivery vectors are based on adeno-associated viruses (AAV). Although these natural viruses are safe and non-pathogenic, they present several barriers that limit their efficacy in delivery as they were not evolved by nature for human therapeutic applications. Directed evolution, a strategy involves the iterative genetic diversification of a molecule to create a gene pool and functional selection to isolate variants with optimal properties, has thereby emerged as a powerful approach for re-evolving AAVs of novel and improved functions. In parallel, recent advances in deep sequencing technologies allow millions of sequences to be assayed and used for training supervised machine learning (ML) models for prediction of protein properties. In this talk, I will be discussing about our work using the combination of directed evolution and ML-guided design to engineer ‘designer’ AAV variants with greatly improved packaging, diversity, and primary human brain infection capabilities. Specifically, we applied such method for developing AAVs that target a crucial cellular component of the central nervous system (CNS), microglia. As a brain-resident macrophage, microglia unfortunately have been implicated in many neurological diseases, such as Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, and others etc. Therefore, genetically manipulating endogenous microglia is a promising therapeutic approach to counteract disease pathology. The extension of such integration of new technologies will have broad utility in the development of next-generation novel vectors for therapeutic applications of many neurological diseases in the near future.
供稿单位 | 学术报告与研讨会授课组
作者 | 汤耀辉
审核 | 丁显廷