Gene editing can treat rare inherited disease

Chinese researchers have reported the first clinical use of a domestically developed RNA-editing technology to treat Duchenne muscular dystrophy, or DMD, a severe inherited disease that causes progressive muscle loss. They also unveiled a significantly upgraded version of the platform that could broaden the future use of RNA-based therapies.

The research team, led by Wei Wensheng of Changping Laboratory and Peking University's School of Life Sciences, published its findings in two papers in the journal Cell on June 10.

The RNA-editing platform, called LEAPER — short for Leveraging Endogenous ADAR for Programmable Editing of RNA — was first developed in 2019. It works by directing naturally occurring enzymes in human cells to correct errors in RNA, the molecule that carries genetic instructions used to make proteins. The latest third-generation version of the technology has improved editing efficiency and accuracy, allowing researchers to target genetic sites that were previously difficult to modify.

"The biggest advantage of LEAPER is that it uses the body's own machinery and does not require the delivery of additional gene-editing enzymes," Wei said.

"This not only simplifies treatment delivery but also reduces the risk of immune reactions and other safety concerns, offering a new option for treating genetic diseases," he said.

Using the technology, the team developed a candidate drug for DMD, a rare inherited disorder that mainly affects boys. The disease causes worsening muscle weakness and often leads to death from respiratory or heart failure in early adulthood.

DMD is estimated to affect about 250,000 people worldwide, including around 70,000 in China, which has the largest patient population. Existing treatments can only slow the disease's progression.

Working with researchers from Kunming University of Science and Technology in Yunnan province, Shanghai Jiao Tong University and other institutions, the team administered the experimental therapy to three pediatric patients.

After a year, all three patients showed sustained improvements in motor function, including stronger respiratory muscles, an important measure of disease progression. No serious adverse events were reported.

"This marks the first time a domestically developed RNA-editing technology has been used in clinical treatment and produced positive results," the researchers said. "It is also the first time globally that RNA editing has been applied to the treatment of DMD."

Wei said gene therapies hold significant potential for treating rare inherited diseases as well as a wider range of medical conditions. His team plans to develop safer, more versatile and precisely controlled therapies to benefit more patients.

wangxiaoyu@chinadaily.com.cn