Zheng-Yi Chen, DPhil, Named Principal Investigator on NIH SCGE $16 Million Grant

October 10, 2024

Zheng-Yi Chen, DPhil, Associate Professor of Otolaryngology–Head and Neck Surgery at Harvard Medical School and investigator in the Eaton-Peabody Laboratories at Mass Eye and Ear, has been named principal investigator of a $16 million National Institutes of Health (NIH) Somatic Cell Genome Editing grant, focused on Investigational New Drug (IND)-enabling studies for platform clinical trials of genome editing in multiple diseases.

This grant will be a collaborative effort across four other institutions in addition to Mass Eye and Ear, including: Roger Hajjar, MD, of Mass General Brigham Gene and Cell Therapy Institute; Yilai Shu, MD, PhD, of Eye & ENT Hospital of Fudan University in Shanghai; Ben Kleinstiver, PhD, of Massachusetts General Hospital; and Xue Zhong Liu, MD, PhD, FACS, of Miller School of Medicine of University of Miami.

Dr. Chen and his team will conduct an IND-enabling study by editing to treat two dominant genetic hearing loss, DFNA41 due to a mutation in the P2RX2 gene and DFNA2A due to a mutation in the KCNQ4 gene.

In DFNA41, hearing loss begins at high frequencies between ages 25 and 35, gradually affecting other frequencies. Initially mild or moderate, the hearing loss becomes severe or profound with time. Patients with DFNA41 are also highly susceptible to noise-induced hearing loss.

In DFNA2A, hearing loss begins within the first two years of life, starting at high frequencies and progressively worsening across other frequencies. This loss also progresses from mild or moderate to severe or profound. Treatment typically involves hearing aids or cochlear implants, depending on the severity of the condition.

The study aims to streamline the regulatory path for editing therapy for genetic hearing loss, with the goal of initiating two clinical trials subsequently.

Following the success of a clinical gene therapy trial in Shanghai, China, conducted in partnership with researchers from Mass Eye and Ear, which demonstrated the restoration of hearing in both ears of children born with genetic deafness caused by mutations in the OTOF gene, this grant further solidifies Dr. Chen’s role as a leading collaborator in expanding CRISPR editing as new treatments for hearing loss.

“Dr. Chen and team’s work is truly transformative, with pioneering clinical trials aimed at reversing hearing loss. As academic researchers, our primary focus is to improve patient outcomes, and these breakthroughs represent the results we are committed to achieving,” said Mark A. Varvares, MD, FACS, William W. Montgomery/John W. Merriam Professor and Chair of Otolaryngology–Head and Neck Surgery at Harvard Medical School and Chair of Otolaryngology–Head and Neck Surgery at Mass Eye and Ear and Massachusetts General Hospital.