Reprogramming and Gene Delivery
This group is taking the lead on transitioning to Phase II, testing candidate genes. They are studying the effects of current transcription factor reprogramming cocktails on supporting cell behavior, including the collection of additional transcriptomic and epigenetic data that will be shared with the CSE group. These experiments are being performed in a variety of systems, including a flattened epithelium guinea pig model that shares features with chronic human deafness. The Groves lab is using transgenic mice to detail the effects of the reprogramming cocktails in the organ of Corti. The Brigande lab is continuing its work on creating efficient mouse model systems to interrogate candidate genes for sensory hair cell regeneration, as pioneered by testing whether viral delivery of these same reprogramming factors is also efficacious. The Raphael lab is taking a similar approach in the guinea pig model, in this case using a virus designed and generated by the Groves and Segil labs. These experiments are part of the group’s broader efforts to develop new methods to deliver molecules and/or genes, for example by endogenous activation of reprogramming factors via CRISPR/cas-9.