Nature medicineMar 3, 2026

Gene editing treatment for inherited high cholesterol: early human trial

CRISPR Gene Editing Weekly Brief ↗PubMed ↗DOI ↗

Updated Jun 28, 2026

Abstract

Essence

An in vivo base-editing therapy lowered PCSK9 and LDL cholesterol in adults with heterozygous familial hypercholesterolemia after a single infusion.

Evidence

This ongoing phase 1 dose-escalation trial reported interim results in 6 adults given single intravenous YOLT-101, finding no grade 3 or higher adverse events and dose-dependent durable reductions in PCSK9 and LDL-C, with 74.4% and 52.3% reductions at 24 weeks in the 0.6 mg/kg cohort (n=3).

Caveat

These are interim phase 1 results from only 6 participants, with the largest efficacy signal coming from a 3-person highest-dose cohort and short-term follow-up focused mainly on safety and biomarker change.

Simplified

Heterozygous familial hypercholesterolemia is a common genetic disorder characterized by lifelong elevation of serum low-density lipoprotein cholesterol (LDL-C) and premature atherosclerotic cardiovascular disease. YOLT-101 is an investigational in vivo gene therapy that uses adenine base-editing technology, delivered via GalNAc-modified lipid nanoparticles to inactivate PCSK9 and achieve sustained LDL-C reduction. Here we report interim results from an ongoing clinical trial evaluating primary (safety and tolerability) and secondary (lowering of PCSK9 and LDL-C levels) outcomes of a single intravenous dose of YOLT-101 in adults with heterozygous familial hypercholesterolemia and uncontrolled LDL-C. Six participants (three men and three women) received escalating doses of YOLT-101 (0.2, 0.4 or 0.6 mg kg). No grade ≥3 adverse events occurred. Transient and self-limited infusion-related reactions and elevations in liver enzymes were the most common adverse events. A single infusion of YOLT-101 induced dose-dependent and durable reductions in circulating PCSK9 and LDL-C, with sustained reductions of 74.4% and 52.3%, respectively, at 24 weeks in the 0.6 mg kgcohort (n = 3), demonstrating promise for future clinical development. ClinicalTrials.gov registration: NCT06458010 . -1 -1

Full Text

Full text is available at the source.

View Full Text ↗

Funding

Competing interests

Competing interests: L.X., X.M., Y. Liu and W.Y. are employees of YolTech Therapeutics. M.O is a member of the advisory board for YolTech Therapeutics. Y. Lu, Z.J.W. and Y.W. are cofounders of YolTech Therapeutics. YOLT-101, the investigational product used in this study, is developed by YolTech Therapeutics. These relationships did not influence the study design, data collection, analysis or interpretation. The other authors declare no competing interests.

PubMed