Boaz P. Levi, PhD- Allen Institute for Brain Science
Bryan B. Gore, PhD- Allen Institute for Brain Science
John K. Mich, PhD- Allen Institute for Brain Science
Tim Jarsky, PhD- Allen Institute for Brain Science
Circuit-selective Whole SCN1A Gene Delivery for Dravet Syndrome
Transformational Science Grant- $500,000 over 3 years
This grant funded with support from Marlins for Mason
Grant Summary from the Investigators:
Dravet syndrome is a severe early infantile epilepsy with no approved disease-modifying therapy, and new therapeutics are urgently needed. In this project, we will test a new therapeutic strategy to deliver to certain brain cells SCN1A, the dysfunctional gene in Dravet syndrome. Whole SCN1A gene delivery has an advantage over the strategies currently being tested in the clinic that increase both the normal and mutant copy of the gene. We will use this grant to 1) measure how Dravet neurons change their gene expression and firing in response to whole SCN1A gene therapy using a new technique called Patch-seq, and 2) we will characterize the effectiveness and safety of whole SCN1A gene delivery in a preclinical mouse model of Dravet syndrome with a missense mutation, a common variant type seen in the human patient population. These studies will pave the way for future therapeutic development.
About the investigators:
Boaz P. Levi is an Associate Investigator in the Human Cell Types group at the Allen Institute where he leads a team with two main objectives: 1) discover cell type-selective enhancers and use them to build enhancer-AAVs to deliver transgene to defined cell types in the brain, and 2) apply those tools to build new therapeutics to cure human diseases including Dravet syndrome. Dr. Levi joined the Allen Institute for Brain Science in 2011. Prior to the Allen Institute, he performed a postdoctoral fellowship in the laboratory of Sean Morrison at the University of Michigan on stem cell self-renewal, and a Ph.D. in the laboratory of Mark Krasnow at Stanford University on airway organ development in Drosophila.
Bryan B. Gore is a Senior Scientist in the Human Cell Types group at the Allen Institute for Brain Science. Dr. Gore leads several therapeutic indications in the Gene Therapy Program, focusing on in vivo modeling of genetic epilepsies, including Dravet Syndrome. Prior to the Allen Institute, he completed a postdoctoral fellowship at the University of Washington where he studied inhibitory control of the dopamine neuron system. Dr. Gore performed graduate studies at Stanford and Genentech on the molecular mechanisms of neural development. Dr. Gore received his Ph.D. in neuroscience from Stanford University, and a BA in English and BS in biochemistry from the University of Washington.
John K. Mich is a Senior Scientist in the Human Cell Types group at the Allen Institute for Brain Science. Dr. Mich is a skilled molecular neuroscientist, leveraging large informatics datasets to develop enhancer-AAV technology and cell type-specific AAV therapeutics for Dravet syndrome and other genetic epilepsies. Prior to joining the Allen Institute, Dr. Mich trained with Sean Morrison in neural stem cell biology and Dr. James Chen in chemical embryology at Stanford University. Tim Jarsky is an Associate Director of the Electrophysiology Department at the Allen Institute for Brain Science. Dr. Jarsky leads a team of scientists working to map and characterize the microcircuits in the mouse and human brain. Dr. Jarsky helped create and leads a pipeline at the Allen Institute to conduct Patch-seq experiments that allow collection of patch-clamp electrophysiology as well as single cell RNAseq from the same cell. These techniques will be critical to establishing effective gene therapies for Dravet syndrome. Prior to joining the Allen Institute, he investigated how synaptic processing and intrinsic membrane properties promote neural information processing. Dr. Jarsky obtained his PhD in neuroscience from Northwestern University, MS in zoology, and BS in biology from the University of Toronto.
