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Deniz Dalkara, M.Sc., Ph.D. - "Cell type specific gene delivery for clinical translation of optogenetics"

Biotherapeutics Department, Institut de la Vision, Paris, France
When Jun 07, 2017
from 12:00 PM to 01:30 PM
Where Tigem Auditorium "Vesuvius"
Contact Name
Contact Phone 081-19230659
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Optogenetics is a biological technique, which uses light to control neurons genetically modified to express light-sensitive membrane proteins. It has become a widely used strategy in research with therapeutic applications ranging from cardiology to neurology. In terms of its clinical application, vision restoration in blind patients has come first due to the existence of an optical window to the retina and thanks to established success of gene therapy in the ocular compartment.  Microbial type opsins as well as vertebrate opsins have shown promise in restoring visual responses in blind rodents and other small animals. However, it was not clear if such treatments can be translated to humans. The major challenges in translating optogenetics from mice to man are related to the lack of optimized viral vectors for targeting various populations of neurons in the primate retina and to the dose extrapolation, going from small animal eyes with minimal immune responses to a large primate eye with immune surveillance. High-level opsin expression is necessary to generate light responses in blind retinas and achieving such expression levels in a large primate eye may come at the expense of a prohibitive viral dose triggering immune responses to both the vector and the transgene. In order to deal with these translational challenges, we studied combinations of adeno-associated virus (AAV) vectors and promoters to target optogenetic proteins to different subsets of neurons in the non-human primate retina. Our data show that successful expression of optogenetic proteins in the primate retina is cell type dependent. Furthermore, we highlight safety and efficacy of optogenetics for cell types that can be efficiently targeted with vector promoter combinations optimized for primates. Challenges remain for targeting certain neuronal populations with existing AAV technologies and for testing functional outcomes in vivo.


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