World's First! Renji Hospital Academician Xia Qiang Team Publishes Nature Medicine Results on In Vivo Liver-Targeted Base Editing for Heterozygous Familial Hypercholesterolemia

Background

Heterozygous familial hypercholesterolemia (HeFH) is a common genetic disorder characterized by lifelong elevation of serum low-density lipoprotein cholesterol (LDL-C) and increased risk of premature atherosclerotic cardiovascular disease. Patients typically require ongoing treatment with medications such as statins and PCSK9 inhibitors, which can involve challenges with long-term adherence and treatment burden.

A research team led by Chinese Academy of Engineering Academician Xia Qiang, president of Renji Hospital affiliated with Shanghai Jiao Tong University School of Medicine, addressed this through the world's first Phase I clinical trial of liver-targeted in vivo base editing gene therapy for HeFH. The interim results were published in Nature Medicine in March 2026.

What was achieved

The trial evaluated YOLT-101, an investigational therapy consisting of an adenine base editor delivered via GalNAc-modified lipid nanoparticles. Six adult patients with HeFH and uncontrolled LDL-C received a single intravenous infusion in a dose-escalation study. In the 0.6 mg/kg high-dose cohort of three patients, serum PCSK9 levels decreased by an average of 74.4% and LDL-C by an average of 52.3% at 24 weeks post-treatment. The lipid-lowering effects were sustained and stable.

Safety results showed no grade 3 or higher adverse events, and no patients withdrew due to adverse events. The study reported no detectable off-target editing. Common first authors included Renji Hospital Liver Surgery Deputy Chief Physician Wan Ping, along with postdocs Siyuan Tang and Dongni Lin, PhD student Mei Long, and Shanghai Jiao Tong University Professor Yuming Lu. Co-corresponding authors were Xia Qiang, Renji's Taihua Yang, East China Normal University’s Yuxuan Wu, and YolTech’s Zijun Wang.

How it works

In HeFH, mutations often affect the LDL receptor pathway in the liver, impairing clearance of LDL-C from the blood. The PCSK9 protein accelerates the breakdown of these LDL receptors on hepatocyte surfaces, resulting in higher circulating cholesterol. The therapy uses a precise adenine base editor to introduce a targeted change in the PCSK9 gene within liver cells, inactivating it and thereby increasing LDL receptor availability for more effective cholesterol removal.

The editing components are packaged in lipid nanoparticles modified with N-acetylgalactosamine (GalNAc). This modification enables specific uptake by hepatocytes through receptor-mediated pathways, achieving dual targeting to the liver. Delivered as a single intravenous infusion, the approach aims to create a durable genetic change in a portion of liver cells without creating double-strand breaks in DNA, differing from traditional CRISPR methods.

What it means for international patients

The trial provides the first human data supporting the safety and potential efficacy of in vivo liver-targeted base editing to achieve sustained reductions in PCSK9 and LDL-C with a one-time infusion. It represents an early step toward possible one-time interventions for certain genetic metabolic conditions currently managed with chronic daily or regular medications. Further studies are needed to establish longer-term outcomes.

Renji Hospital maintains an International Medical Center, primarily at its East Campus in Pudong, which has served patients from more than 40 countries and regions. Services include multilingual support with English, DNV GL international accreditation for certain programs, and partnerships with over 30 international insurance providers for direct billing. It is designated as one of Shanghai’s pilot public hospitals for international medical tourism. Patients should contact the hospital’s international department directly to confirm any eligibility, availability, or participation criteria for related research or care, as these must be assessed individually.

About the hospital

Renji Hospital, founded in 1844, was Shanghai’s first hospital to practice Western medicine. It is a Grade 3A comprehensive tertiary hospital affiliated with Shanghai Jiao Tong University School of Medicine, operating four campuses with approximately 2,250 beds. The hospital is a national leader in organ transplantation and holds multiple national key clinical specialty designations, including in liver surgery, gastroenterology, urology, reproductive medicine, and rheumatology.

Under Academician Xia Qiang, its Liver Surgery department has become the world’s largest center for pediatric liver transplantation, having performed thousands of procedures with reported 1-year and 5-year survival rates reaching international advanced levels. The International Medical Department provides dedicated services for foreign patients, including coordinators and alignment with international care standards.