Grant Award Details
- To design and test, in rats and in patient-derived iPSC neurons, a Cas13 (RNA nuclease)-mediated gene therapy approach for Angelman syndrome (AS) in which the paternal UBE3A antisense RNA, which is expressed in neurons, is cleaved in such a way that paternal UBE3A expression is activated without activating other transcripts repressed by the antisense RNA.
Grant Application Details
- AAV9-Cas13 gene therapy for Angelman syndrome
AAV9-Cas13 gene therapy for Angelman syndrome using a first-in-kind mechanism of action that will safely and permanently restore expression of endogenous UBE3A that is deficient in CNS neurons.
Angelman syndrome is a rare (1 in 15,000 births) neurogenetic disorder caused by loss of UBE3A in the brain, causing severe developmental delay, ataxia and epilepsy. There are no treatments or cures.
Major Proposed Activities
- Determine the optimal Cas13 guide-RNA for a rodent model.
- Determine the optimal Cas13 guide-RNA for a humans.
- Show that the gene therapy improves gene expression in rodent models.
- Show that the gene therapy improves gene expression in human cells.
- Show that the gene therapy improves symptoms in rodent models.
- Show that the gene therapy can be safe and permanent.
In addition to directly benefiting the ~2,500 children and families living with Angelman syndrome in California, this gene therapy with a first-in-kind mechanism of action could bring new treatments and new opportunities to our state. California has long been a hub of innovation, and creates an environment in which new technologies can be born, fostered, and attract others who want to create a better future for our residents. This activity will help train some of them, and inspire many others.