School of Biomedical Sciences cordially invites you to join the following seminar:

Speaker: Dr. Zongli Zheng, Associate Professor, Department of Biomedical Sciences, City University of Hong Kong
Talk Title: PAM-Mediated Precise Gene Editing and In Vivo Delivery of the CRISPR-Cas System

Date: 3 September 2025 (Wednesday)
Time: 4:00 pm – 5:00 pm
Venue: Lecture Theatre 1, G/F, William M.W. Mong Block, 21 Sassoon Road 
Host: Professor Michael Hӓusser

Biography

Dr. Zheng received his PhD with distinction from Karolinska Institutet and completed his postdoctoral training at Harvard Medical School. He is currently an associate professor at City University of Hong Kong. Dr. Zheng invented AMP technology, which has been globally adopted in molecular diagnostic assays to guide targeted therapy. He co-led the development of the GUIDE-seq method, widely used for genome-wide unbiased profiling of CRISPR edits, supporting the first CRISPR therapy approved by the FDA in December 2023. Currently, his lab focuses on genomic medicine and biotechnology innovation to enhance our understanding, diagnosis, and treatment of diseases. Their research interests include lung cancer, precision genome editing and delivery technologies, and liquid biopsy. Dr. Zheng has published 65 papers, including as a first or corresponding author in prestigious journals such as Nature Medicine, Nature Biotechnology, Nature Biomedical Engineering, Gastroenterology, Journal of Thoracic Oncology, Clinical Cancer Research, and PNAS, accumulating over 18,000 citations.

Abstract

The correction of disease-causing mutations in relevant organs using CRISPR-Cas nucleases may offer "one-and-done" curative solutions for disease treatment. The first step in engaging in a DNA target site for prokaryotic CRISPR-Cas nucleases is the recognition of protospacer adjacent motifs (PAMs). PAM-mediated specific editing of disease-causing alleles is a promising approach for treating genetic diseases, but it requires a rich set of specialized PAMs. Characterizing the PAM requirements of different Cas enzymes is a bottleneck in the discovery of Cas proteins in mammalian cell contexts. To address this challenge and enable more scalable characterization of PAM preferences, we have developed a method called GenomePAM, which allows for direct PAM characterization in mammalian cells. By applying GenomePAM in a metagenomic study, we identified a set of new Cas nucleases with diverse PAM recognition profiles. I will discuss their utility in the precise editing of two disease gene alleles.

Furthermore, the in vivo delivery of the CRISPR-Cas system to desired tissues is a major challenge in realizing the system's full potential. Current in vivo genome editing approaches based on viral vectors risk prolonged off-target editing and genomic integration, while non-viral approaches have limited tissue specificity. Using inherited corneal dystrophies—currently untreatable—as an example, we address these in vivo genome editing limitations with an engineered protein-delivery vehicle (PDV). PDV combines the tissue tropism capabilities of viruses with the ready-to-act and transient CRISPR-Cas9 ribonucleoprotein (RNP). We demonstrate a potentially clinically viable approach for in vivo gene editing using PDV-delivered Cas9-RNP.

ALL ARE WELCOME.