World's First Gene-Editing Therapy for Hyperlipidemia Approved

The Breakthrough in Genetic Therapy for Hyperlipidemia

On November 6, 2025, Shanghai's CorrectSequence Therapeutics Co., Ltd. (Correctseq) made history by announcing the completion of dosing in its first patient for a cutting-edge gene-editing therapy aimed at alleviating hyperlipidemia, specifically for those suffering from APOC3-driven conditions. This landmark achievement not only showcases the company's innovative approach using transformer Base Editing (tBE) technology but also holds the promise of a long-term solution for patients afflicted by severe metabolic disorders.

The First Patient's Journey

The patient, diagnosed with chylomicronemia—a severe metabolic disorder characterized by abnormally high triglyceride levels—had been plagued with fasting triglyceride (TG) levels exceeding 12.5 mmol/L along with recurrent acute pancreatitis. Under the investigator-initiated trial (IIT) for CS-121 therapy, the individual received a single low-dose intravenous treatment. Astonishingly, within three days post-administration, there was a marked decrease in fasting TG levels, pointing towards significant efficacy without any adverse side effects recorded during or after the treatment.

This successful therapy is groundbreaking as it represents the first clinical application of gene editing focused on combating hyperlipidemia globally. Chylomicronemia elevates the risk of severe health complications, particularly acute pancreatitis, making the search for effective treatments imperative.

Understanding Hyperlipidemia and APOC3

Hyperlipidemia, particularly in its chylomicronemia form, poses a serious health threat characterized by excessive triglyceride accumulation. Current methods to manage this condition mainly focus on dietary restrictions and existing medications, which often fail to produce effective results due to their limited efficacy and patient compliance issues.

APOC3, a protein produced in the liver, is integral to the metabolism of triglycerides. Research indicates that individuals with natural mutations resulting in reduced APOC3 functionality experience lower triglyceride levels without significant adverse effects. With advancements in gene-editing technology, Correctseq has now implemented a method to therapeutically modulate APOC3 expression at the genetic level, which presents a potential curative pathway for individuals with chylomicronemia and hypertriglyceridemia.

CS-121 Therapy: A Revolutionary Approach

The CS-121 therapy developed by Correctseq utilizes next-generation transformer Base Editing (tBE) to achieve precise genetic modifications. This method is administered via lipid nanoparticle (LNP) delivery systems, which target the liver effectively, correcting the APOC3 gene specifically. By emulating beneficial mutations that mitigate APOC3 activity, it effectively lowers plasma triglyceride levels and tackles the disease at its root cause.

One of the most significant advantages of the tBE technology is its ability to correct individual bases without causing double-strand DNA breaks, thereby minimizing safety risks commonly associated with CRISPR-based therapies. Preclinical studies have shown impressive safety and efficacy results, with no off-target effects noted across various organs including the liver, lungs, and heart.

Future Implications of Gene Editing

The first patient, a 63-year-old man, showcased promising results with the therapy. His triglyceride levels notably dropped three days following the treatment. Furthermore, his hospital discharge occurred three days post-treatment, and until now, he hasn't exhibited any treatment-related side effects.

Leading the research behind CS-121, Professors Huan Zhou and Zhili Wu from the First Affiliated Hospital of Anhui Medical University expressed hope that this innovative therapy could herald a new era of one-time treatment options offering lifelong effectiveness for patients suffering from hyperlipidemia and other metabolic disorders.

In conclusion, as Correctsequence Therapeutics continues to pioneer new research in this space, their cutting-edge CS-121 therapy not only stands to revolutionize treatment for hyperlipidemia but also illustrates the broader potential of gene editing as a viable therapeutic option for a variety of genetic and metabolic disorders. Their past success with CS-101 for treating β-thalassemia demonstrates their commitment and capability to drive biotechnology forward and establish a legacy of transformative medical treatments.

For further insights about CorrectSequence Therapeutics, visit their website: www.correctsequence.com