Awardees

Yasaman Gholamalipour  |  Aronin Research Group |  Huntington’s Disease Society of America Berman-Topper Fellowship

CRISPR-Cas9 genome editing is a promising technology with the potential to treat genetic diseases by changing the DNA mutation that is the underlying cause of the disease. HD is caused by a CAG repeat expansion in Exon 1 of the Huntingtin gene. Our goal is to apply CRIRSPR-Cas9 genome editing tools to correct the mutant Huntingtin gene back to the wild type gene by reducing the number of CAG repeats to below the pathogenic threshold. We have very promising results in HD patient cells, and we are currently working on making the method work more efficiently in animal models. In one line of experiments, we are working on modulating cellular DNA repair pathways to probe the mechanism of induced repeat length contractions and identify reagents to improve this activity in the brain. Additionally, current approaches for delivery of these gene editing tools to the brain have challenges such as safety concerns due to continuous expression of these gene editing complexes. Therefore, we are concurrently, developing a new technique to deliver CRISPR-Cas9 gene editing tools to the brain in the form of ribonucleoprotein (RNP) complexes. This method will potentially reduce safety concerns due to short half-life of RNPs and promote uptake and distribution of editing throughout brain. If successful, a single treatment could revert the CAG repeat in mutant Huntingtin gene to the normal range. This approach will have therapeutic uses for HD and other neuropathological disorders associated with trinucleotide repeat expansions.