Background

Snijders Blok-Campeau Syndrome (SBCS) is a rare neurodevelopmental disorder caused by mutations in the CHD3 gene, a chromatin remodeling factor. Individuals with this condition often experience cognitive impairment or language delays. However, it is generally not life-threatening. In the field of gene therapy, the third-generation gene editing technology, CRISPR-Cas9, has been widely used to cleave target genes. However, this technology is prone to off-target effects, which can lead to unintended DNA cleavage or chromosomal rearrangements.

Consequently, base editing (BE) technology, which precisely corrects single DNA bases, has gained attention. In particular, rare central nervous system diseases pose significant challenges for therapeutic development, creating a strong need for personalized treatments. China, after the He Jiankui incident in 2018, which involved germline gene editing and shocked the world, claimed to have significantly strengthened its oversight of gene therapy clinical trials. However, the regulatory gaps in clinical trials conducted individually at university-affiliated hospitals remain unresolved.

Key Findings

A research team led by Professor Zilong Qiu from the Department of Neurology at the Shanghai Jiao Tong University School of Medicine's Xinhua Hospital attempted gene therapy on a 6-year-old girl named 'Mei' (pseudonym) who suffers from SBCS. The team prepared a customized BE therapeutic to correct the patient's mutated CHD3 gene sequence. To deliver the therapeutic to the target area in the brain, they directly injected a large number of adeno-associated virus (AAV) vector particles into the patient's cerebrospinal fluid at the base of the spinal cord. This is poised to be recorded as the world's first in vivo BE clinical trial targeting the central nervous system. The patient's parents donated more than $800,000 (approximately 1.1 billion Korean Won) to support the development of a personalized therapy for their child.

However, shortly after the administration, the patient experienced an acute immune response and died within a week. This tragedy, which occurred in March 2025, was kept hidden for over a year. In fact, the researchers did not mention the patient's entry into the clinical trial or their death in any of the animal experimental result papers they published in the international journal Nature. The cover-up, which compromised the transparency of the research, was finally revealed through a joint investigation by the journals Science and Retraction Watch, a watchdog for retracted papers. In response to the growing controversy, Shanghai Jiao Tong University School of Medicine announced an official investigation and promised to prevent recurrence.

Significance and Prospects

This incident raises serious concerns about the safety and ethical oversight of BE, a next-generation gene editing technology. BE is often considered safer than conventional CRISPR technology because it does not cleave double-stranded DNA. However, this tragedy has demonstrated that directly administering high concentrations of AAV vectors into the cerebrospinal fluid can place an overwhelming burden on the patient's immune system. It clearly shows that the safety validation of the gene delivery vector is as important as the precision of the technology.

Furthermore, the governance issues surrounding N-of-1 trials, which are designed for a single patient, have come to light. The practice of patients' families directly funding research can be a driving force in the development of treatments for rare diseases. However, if this becomes a way to bypass rigorous scientific validation or ethical review, it can lead to adverse effects that threaten the lives of clinical trial participants. In particular, China's academic community, which boasts world-class gene editing technology, is facing criticism for failing to keep pace with the rapid development of technology in terms of transparency and ethical awareness.