Targeted modifying the human SNCA intronic enhancer as gene therapy for Parkinson’s disease

• Applicant: Fubo Cheng, Ph.D.
• Subject Area: Molecular and Cellular Neurology and Neuropathology
• Term: since 2024
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 547313212

Our previous report using different cellular and animal models revealed the crucial role of SNCA intronic enhancers in regulating its expression. As increased dosage of SNCA contributed to PD pathogenesis and the severity of clinical phenotypes also correlate with the number of SNCA copies, targeting SNCA intronic enhancer to repress its expression could be used as treatment of PD. With this application we will perform a series of studies to characterize the treatment prospect, as well as off-target side-effect of targeted editing the SNCA intronic enhancer (SNCA En-2) by a dual virus based split dCas9-repressor compound and by a Cas9 mediated enhancer deletion complex for PD. Eventually through this project, the therapeutic prospect of two treatments by targeted editing SNCA En-2 will be thoroughly characterized both in vitro and in vivo, which will provide pre-clinical evidence for their application on PD patients.

• DFG Programme: Research Grants