HuidaGene reports child’s death after high-dose AAV vector administration in Duchenne CRISPR therapy trial
HuidaGene reports child’s death after high-dose AAV vector administration in Duchenne CRISPR therapy trial
In August 2025, a participant in the high-dose group of HG302-01 died. On August 5, HuidaGene publicly disclosed the event for the first time and attributed the death to an inflammatory response following systemic administration of the AAV vector.
Duchenne muscular dystrophy is caused by mutations in the DMD gene. These mutations prevent muscles from producing dystrophin, a protein that helps muscle fibers withstand contraction. In the HG302 therapy, a CRISPR editor is intended to modify a region of DNA in muscle cells and restore dystrophin production. An AAV vector, a delivery vehicle derived from a virus, carries the editor through the bloodstream to the tissues.
HG302-01 is an early trial involving four boys from four to eight years old. According to the trial registry, each participant received a single intravenous injection at either a low or high dose. The protocol assigns the first 26 weeks to assessing the frequency and severity of systemic adverse reactions. HuidaGene reports that the other three participants remain under long-term follow-up.
A high dose of AAV circulates through the bloodstream throughout the body. Complement, a group of proteins in the blood, recognizes foreign particles, while cytokines transmit inflammatory signals to cells. HuidaGene states:
“Based on the available clinical and scientific evidence, the participant developed acute respiratory distress syndrome in the setting of marked complement and cytokine activation following systemic administration of a high dose of AAV.”
In this syndrome, inflammation in the lungs prevents enough oxygen from entering the bloodstream. A 2023 review describes other programs using high-dose systemic AAV delivery that caused severe immune toxicity, including complement activation and ARDS.
CRISPR and AAV address different engineering problems. CRISPR determines where the DNA is edited, while AAV delivers the editor to the tissues. HuidaGene attributes the death to the delivery step. Following systemic administration of a high dose of the vector, the participant developed ARDS in the setting of severe complement and cytokine activation. In future trials, the vector dose, immune response, and lung inflammation will be as important as editing accuracy.