image: The project team led by Professor Zheng Zongli (right) of CityUHK’s Department of Biomedical Sciences, will focus on liver and cardiovascular genetic diseases, harnessing state-of-the-art “DNA surgery” technology to develop two core therapeutic medicines and advance them into clinical trials.
Credit: City University of Hong Kong
Genome editing is increasingly recognised as a leading frontier in biomedical research and an essential driver of healthcare innovation. At City University of Hong Kong (CityUHK), a research team has been awarded funding under the “RAISe+ Scheme” launched by the Government of the Hong Kong Special Administrative Region of the People’s Republic of China to conduct a project applying novel genome editors in clinical trials over the next three years.
The team will focus on liver and cardiovascular genetic diseases, harnessing state-of-the-art “DNA surgery” technology to develop two core therapeutic medicines and advance them into clinical trials. The project aims to create “one-and-done” therapies that are safe, efficacious, and affordable, ultimately introducing new treatment to patients in Hong Kong and globally who suffer from inherited diseases.
The project, titled “In Vivo Somatic Human Genome Editing to Cure Genetic Diseases: Transforming Novel Genome Editors and Engineered Delivery Vehicles to Clinical Trial”, was awarded to a team led by Professor Zheng Zongli of the Department of Biomedical Sciences, CityUHK. It aims to create safe, efficacious, and specific genome editors that can perform DNA surgery on human somatic cells for testing in Phase I clinical trials.
More Durable than Traditional Gene Therapy
The dawn of a new era of “DNA surgery” commenced in 2023 when the U.S. Food and Drug Administration (FDA) approved Casgevy, the first-ever genome editing therapy. This kind of technology treats diseases by directly correcting errors in a patient’s DNA. Scientists use tools to precisely cut, remove, or replace faulty parts of the genes, allowing cells to function normally again and preventing the production of harmful proteins. Engineered lipid nanoparticles (eLNPs) are used as delivery vehicles to transport “DNA surgery” tools accurately into the target cells to perform DNA editing.
However, many challenges must be addressed before such therapies can be broadly applied, particularly with respect to safety, precision, and durability. About 25% of genetic diseases are autosomal dominant (meaning that inheriting just one faulty copy of the gene from either parent is enough to cause the disease), where mutated genes continuously produce harmful proteins. These conditions cannot be cured by traditional gene therapy approaches, which typically require repeated or lifelong dosing and whose efficacy diminishes over time.
The CityUHK team’s project directly addresses this unmet need. By leveraging the Nobel Prize-winning CRISPR genome editing platform, the team can perform “DNA surgery” on somatic mutations in patients carrying genetic diseases. Their solution also incorporates the team’s patented high-fidelity nucleases, which can be efficiently delivered into target cells using their engineered lipid nanoparticles (eLNPs), thereby improving delivery and reducing the likelihood of off-target DNA cuts. In addition, the team develops a proprietary gene off-target profiling system to sensitively detect off-target edits. Since the “DNA surgery” occurs at the DNA level and can be passed on to new cells, this approach provides a durable and long-lasting solution, eliminating the need for repeated medications.
New drug pipelines for liver and cardiovascular disease
The team is developing two drug candidates – PL-100 for a rare genetic disease of the liver and PL-200 for cardiovascular disease, which presents a major burden for global health care systems. Both candidates are at the stage of entering IND (investigational new drug) enabling studies and initiating investigator-initiated clinical trials.
Preliminary pre-clinical studies in non-human primates have already been completed. The team’s high-precision genome editor and high-efficiency delivery vehicles can match industry-leading efficacy at lower dosages. Next, the team will seek pharmaceutical partnerships or pursue in-house development to bring both candidates into clinical trials.
“Genome editing represents the next frontier in medicine, not merely controlling diseases but curing them at their root. Our mission is to develop therapies that are safe, affordable, and life-changing for patients,” explained Professor Zheng. “Given Hong Kong’s talent pool, infrastructure, and strong policy support, the city has the potential to become a global leader in genomic medicine. We are grateful to CityUHK, the funding support under the RAISe+ Scheme, and our investors. We are honoured to contribute,” he added.