Chinese researchers treat rare disease with RNA editing technology

A team of Chinese researchers has treated the severe and rare hereditary disease Duchenne muscular dystrophy (DMD) using a novel RNA editing technology called LEAPER, with details of the technology and its clinical application published on Wednesday in the journal Cell. This marks the first time an RNA editing technology developed by China has entered the clinical trial stage, and also the first time globally that RNA editing has been applied in the treatment of DMD. DMD is caused by a gene mutation, with symptoms including progressive muscle atrophy and loss of motor function. Patients typically begin showing symptoms in childhood, gradually lose the ability to walk, and most die prematurely from respiratory or heart failure. Although classified as a rare disease, China has one of the largest DMD patient populations in the world due to its vast population base. Current treatments can only partially delay disease progression but cannot reverse it. DMD is also widely recognised as one of the most challenging diseases in the field of gene therapy. The disease-causing gene is too large for conventional gene therapy methods to introduce the whole gene into the patient’s body. Moreover, different patients can carry more than 7,000 types of pathogenic mutations, meaning a single treatment regimen often only reaches a small fraction of patients. Developing a treatment strategy that combines broad applicability with long-term efficacy therefore remains a major challenge for the global medical community. The latest RNA editing technology was developed by a team from the Beijing-based Changping Laboratory and Peking University. According to team leader Wei Wensheng, components of the LEAPER system can accurately identify the faulty genetic blueprint in muscle cells, repair the gene by deleting specific sequences, and enable cells to produce functional protein according to the corrected genetic blueprint, thus helping muscles restore their vitality. Unlike traditional approaches, the new technology does not require delivery of exogenous editing enzymes. Using only a single segment of modified RNA molecule, it can mobilise key enzymes naturally contained within human cells to achieve accurate editing of target RNA. The system is simple, offers high safety, and minimises the delivery burden. The team collaborated with Kunming University of Science and Technology in southwest China, Shanghai Jiao Tong University in east China, and other institutions to develop a drug candidate. Three child patients who underwent treatment all showed significant and sustained improvement in motor function over a one-year follow-up period. Xie Xiaoliang, director of the Changping Laboratory and an academician at the Chinese Academy of Sciences, said the development and application of the LEAPER platform reflects the laboratory’s commitment to developing new drugs through original basic research and cutting-edge technology. He expressed hope that the new technology can benefit an increasing number of patients suffering from serious diseases.