Directed Evolution of Novel AAV Vectors for Clinical Gene Therapy скачать в хорошем качестве

Directed Evolution of Novel AAV Vectors for Clinical Gene Therapy

Presented By: David Shaffer, PhD Speaker Biography: David Schaffer's research program employs molecular and cellular engineering approaches to investigate biomedical problems. In particular, their lab focuses on the related areas of gene therapy, genome editing, and stem cell bioengineering, with applications to diseases of the nervous system and other tissues. They are using high throughput protein engineering approaches to engineer safe, targeted viral gene delivery vehicles for gene therapy, and technologies developed in their lab are in numerous human clinical trials. Furthermore, they are developing novel technologies to investigate and better control the behavior of stem cells, both to advance basic biological knowledge of the development and function of the nervous system and to engineer stem cell based therapies to treat neurodegenerative disease. Webinar: Directed Evolution of Novel AAV Vectors for Clinical Gene Therapy Webinar Abstract: Gene therapy has experienced an increasing number of successful human clinical trials, leading to 6 FDA approved products using delivery vectors based on adeno-associated viruses (AAV). These successes were possible due to the identification of specific disease targets for which natural variants of AAV were sufficient. However, vectors face a number of barriers and shortcomings that preclude their extension to most human diseases, including limited delivery efficiency to target cells, pre-existing antibodies against AAVs, suboptimal biodistribution, limited spread within tissues, and/or an inability to target delivery to specific cells. These barriers are not surprising, since the parent viruses upon which vectors are based were not evolved by nature for our convenience to use as human therapeutics. Unfortunately, for most applications, there is insufficient mechanistic knowledge of underlying virus structure-function relationships to empower rational design improvements. As an alternative, for over two decades we have been implementing directed evolution – the iterative genetic diversification of the viral genome and functional selection for desired properties – to engineer highly optimized, next generation AAV variants for efficient and targeted delivery to any cell or tissue target. We have genetically diversified AAV using a broad range of approaches from fully random (e.g. error prone PCR) to computationally guided (e.g. by machine learning). The resulting large (~109) libraries are then functionally selected for substantially enhanced delivery, yielding AAVs capable of highly efficient therapeutic gene delivery. Our variants have been effective in both animal models and in 6 human clinical trials to date, and results from both will be discussed. Earn PACE Credits: 1. Make sure you’re a registered member of Labroots (https://www.labroots.com/) 2. Watch the webinar on YouTube or on the Labroots Website (https://www.labroots.com/ms/webinar/d...) 3. Click Here to get your PACE credits (Expiration date – October 23, 2026): (https://www.labroots.com/credit/pace-... Labroots on Social: Facebook:   / labrootsinc   Twitter:   / labroots   LinkedIn:   / labroots   Instagram:   / labrootsinc   Pinterest:   / labroots   SnapChat: labroots_inc