Research on genome editing for treating long QT syndrome has incredible potential

Long QT syndrome (LQTS) is a heart rhythm disorder that causes fast, chaotic heartbeats, affecting the electrical signals that travel through the heart and cause it to beat. LQTS is one of the main congenital cardiac diseases caused by gene mutations. Patients left without therapy experience a high mortality rate and new, more targeted therapies are needed.

Research led by Hua Zhu, PhD, professor of cardiac surgery at The Ohio State University College of Medicine, found that prime editing, a new technology that works like a “search-and-replace” genome editing technology for DNA, can directly write new genetic information into a targeted DNA site.

“We identified novel 1693G-C point mutation in the KCNH2 potassium channel,” Dr. Zhu says. “Prime editing can be used to treat KCNH2 mutation.”

Thomas Hund, PhD, professor of Internal Medicine and Biomedical Engineering at The Ohio State University, is the director for the Dorothy M. Davis Heart and Lung Research Institute (DHLRI). He says although this project is in early stages, Dr. Zhu’s research has a high ceiling in terms of impact.

“It could be a great application of gene editing for human arrhythmia and potential for interaction between the university’s DHLRI and Gene Therapy Institute,” Dr. Hund says.

Earlier research by Dr. Zhu and his team examined the efficacy of conventional CRISPR-Cas9-mediated gene editing approaches. The advantage of prime editing is that it combines the powerful DNA-scanning and sequence-identification capabilities of the CRISPR-Cas9 system with a reverse transcriptase enzyme, which uses an RNA template to synthesize a new single-strand DNA sequence and insert it into the DNA.

“Prime editing is considered to have a very desirable safety profile when compared to conventional CRISPR-Cas9-mediated gene editing approaches,” Dr. Zhu says. “It provides exciting advancements in the studies of the molecular causes of human diseases.”