Hui-Gene Reports First-in-Human Clinical Data for HG302 in Cell: Molecular Activity and Key Safety Findings in CRISPR-Based Gene Editing for Duchenne Muscular Dystrophy

Four boys with Duchenne muscular dystrophy received an experimental gene-editing therapy. Two walked farther. One died.

The results, published online October 26 in the journal Cell, mark the first published clinical data for an in vivo CRISPR-based therapy administered systemically for DMD. They offer molecular proof that gene editing can work inside human muscle—but also expose the limits of current safety models for whole-body delivery of adeno-associated virus vectors.

Hui-Gene Therapeutics, a Shanghai-based gene therapy company, announced the findings from its investigator-initiated first-in-human trial, HG302-01. The study enrolled four ambulant male DMD patients who received a single intravenous infusion of HG302 at one of two dose levels: 5.0×10¹³ vg/kg or 1.0×10¹⁴ vg/kg.

Muscle biopsies taken after treatment showed targeted gene editing at the intended site and detectable dystrophin protein expression—the protein whose absence causes the disease. That molecular activity is the central proof-of-concept the field has been waiting for.

The two subjects who completed 12 months of follow-up showed functional gains. One improved by 8 points on the North Star Ambulatory Assessment, a standardized measure of motor function in DMD, and increased his six-minute walk distance by 106 meters. The other gained 10 points on the same scale and walked 162 meters farther in six minutes.

But the fourth subject—the last patient scheduled to receive treatment in the trial—developed a fatal serious adverse event that was assessed as treatment-related. He suffered acute respiratory distress syndrome in the setting of significant complement activation and a systemic inflammatory response. The paper details the clinical course, safety investigations, and causality assessment.

Dosing in the trial is now complete. The remaining three subjects continue in long-term safety follow-up.

The findings underscore a persistent challenge in the field: existing preclinical models and risk-mitigation strategies have limited ability to predict or prevent severe immune-mediated toxicities from systemically administered AAV vectors. The authors call for continued refinement of safety assessment and clinical monitoring protocols.

HG302 has received orphan drug designation from the U.S. Food and Drug Administration. It is built on Hui-Gene's HG-PRECISE® gene editing platform, which combines proprietary CRISPR technology with artificial intelligence.

Duchenne muscular dystrophy is a rare, progressive genetic disorder caused by mutations in the DMD gene that result in absent or nonfunctional dystrophin. The disease primarily affects skeletal and cardiac muscle, leading to progressive loss of strength and function. Current treatments can manage symptoms and slow some disease progression, but there is no cure.

The full paper, titled "In Vivo Genome-Editing Therapy for Duchenne Muscular Dystrophy: Preclinical Studies and First-in-Human Trial," is available in Cell.

More information about Hui-Gene Therapeutics is available at www.huidagene.com.