My CIRM SPARK Internship

Over the summer, I interned in the Fink Lab at the UC Davis Insititute of Regenerative Cures through the CIRM SPARK program. The Fink Lab is focused on developing therapeutic applications for genetically-linked neurologic diseases. When I was given the details of the research project I would be working on, a wave of excitement ran through me because this project related to my neurodiversity interests. Today, I will be explaining my research project: Syngap1 upregulation using split dCas9 activators in dual AAV vectors.

SYNGAP1-related intellectual disability is a rare syndrome, accounting for about 1 to 2 percent of intellectual disability cases. Symptoms of the syndrome include seizures, delayed development of speech and motor skills, behavior disorders, and sleep disorders. SYNGAP1 is a haploinsufficient gene, meaning that when one copy of the gene is mutated, not enough protein is produced. In this case, an insufficient amount of SynGAP protein is produced. Our solution was to upregulate the expression of the SYNGAP1 gene to produce a sufficient amount of protein for proper neuronal function. 

You must have heard of CRISPR-Cas9 by now. CRISPR is a gene-editing tool, where there is a guide RNA that goes to the specified location of the gene and Cas9 makes a cut in the DNA. This can help fix mutations that cause a variety of disorders. For my project, I used dead Cas9, meaning that it does not make a cut in the DNA. Since the goal was to upregulate expression of the gene, we used a transcriptional activator which binds to the stem loops of the guide RNA. This attracts the RNA polymerase to come to this gene of interest and transcribe the DNA to make more copies of the protein.