Dr. Segal’s research, together with the labs of Kyle Fink and Jill Silverman, focuses on developing molecular therapies for neurologic disorders. We use programable DNA- or RNA-binding platforms (Zinc finger, TALE, CRISPR/Cas9, Cas12, Cas13) to cause long-term changes in the expression of disease genes. This approach avoids problematic double-strand breaks. We use a variety of delivery systems (protein, AAV, lipo-particles, stem cells) to treat the brain in animal models of disease, which are extensively characterized on a molecular and behavioral level. A flagship project is Angelman syndrome, for which the therapeutic strategy is to reactivate a silenced gene in the brain. We collaborate with groups around the world to de-risk genetic therapies for this and several other related disorders.