Preclinical assessment of CRISPR-mediated gene regulation to rescue haploinsufficiency in Pitt Hopkins syndrome

Kyle Fink, PhD, Principal Investigator

University of California Davis Medical Center

$114,030

AND

Gad Vatine, PhD, Principal Investigator

Ben Gurion University of the Negev, Israel

$70,000

2022

The ultimate goal is to pre-clinically examine CRISPRa as a potential treatment for PTHS patients.

Specific aims:
1. Test the molecular profile and functional performance of patient-derived TCF4-haploinsufficient neural cells (Vatine lab).
2. Establish a PTHS-Brain-on-Chip (BoC) platform (Vatine lab).
3. Identify lead sgRNAs that upregulate TCF4 when paired with CRISPR activator effector domains in a human cell line (Fink lab).
4. Evaluate TCF4 gene regulation with lead CRISPRa constructs in the patient derived platforms (Vatine and Fink labs).
5. Examine the off-target profile of CRISPRa for TCF4 (Fink lab).