The patient, diagnosed with chylomicronemia, had a long history of fasting triglyceride (TG) levels exceeding 12.5 mmol\/L and recurrent acute pancreatitis. In the dose-escalation IIT for CS-121, his fasting TG level dropped significantly within three days after a single low-dose administration, with no adverse events<\/b>.<\/p>\n
This is the world’s first successful clinical treatment of hyperlipidemia with the gene-editing therapy targeting APOC3<\/i><\/b>.<\/p>\n Picture:<\/b> The world’s first patient of the gene-editing therapy targeting APOC3<\/i> (Correctseq’s CS-121) for hyperlipidemia (the 6th from the right) has successfully completed dosing and been discharged.<\/p>\n Chylomicronemia is a metabolic disorder characterized by abnormally elevated chylomicrons in the blood, associated with lipid metabolism dysfunction, leading to extremely high fasting TG levels and potentially life-threatening complications such as acute pancreatitis. It is the most severe subtype of severe hypertriglyceridemia (sHTG)<\/b>, including Familial Chylomicronemia Syndrome (FCS)<\/b> and Multifactorial Chylomicronemia Syndrome (MCS)<\/b>. FCS<\/b> is a rare autosomal recessive disorder caused by biallelic mutations in the Lipoprotein Lipase (LPL) gene or other key regulatory genes, with fasting TG \u226510 mmol\/L (885 mg\/dL) and a global prevalence of 1 in 100,000\u20131,000,000. MCS<\/b> results from a complex interaction of genetic, lifestyle, or metabolic disorders with a prevalence as high as 1 in 600 worldwide.<\/p>\n Current treatments for chylomicronemia primarily aim to control fasting TG levels below the acute pancreatitis risk threshold (<5.7 mmol\/L or 500 mg\/dL), but available triglyceride-lowering medications are often insufficient, and very-low-fat diets are hard to maintain in a long-term manner.<\/p>\n Scientific studies have shown that the APOC3 protein, produced in the liver, plays a central role in TG regulation. Large-scale population analyses have shown that individuals carrying natural APOC3 loss-of-function mutations have significantly lower TG levels without adverse effects. With advances in gene-editing technologies, it is now possible to therapeutically modulate APOC3 expression at the genetic level to lower TG levels \u2014 offering a potential curative strategy for chylomicronemia and hypertriglyceridemia.<\/p>\n CS-121, Correctseq’s first in vivo<\/i> gene-editing <\/b>therapy<\/b> for chylomicronemia and hypertriglyceridemia, is based on the transformer Base Editor (tBE)<\/b> \u2014 a highly precise base-editing system independently developed by Correctseq’s scientific co-founders. Administered via intravenous injection, tBE is delivered via lipid nanoparticles (LNPs) to the liver and precisely edits the target APOC3<\/i><\/b> gene. It mimics beneficial natural APOC3<\/i> loss-of-function variants to downregulate APOC3 expression and effectively lower plasma TG levels. By addressing the disease at the genetic level, this therapy aims to achieve “one-time treatment, lifelong efficacy<\/b>.”<\/p>\n CS-121 utilizing the next-generation tBE technology, which enables precise single-base correction without DNA double-strand breaks, offering superior safety over the gene-editing therapies based on CRISPR. tBE avoids potential safety risks such as p53 activation, chromosomal damage, off-target effects, and liver toxicity caused by DNA double-strand breaks. Preclinical animal studies showed excellent safety and long-term efficacy, with no off-target editing detected in various organs including liver, lungs, muscle, spleen, ovaries, heart, and kidneys.<\/p>\n The first patient, a 63-year-old male, received a single low-dose intravenous administration on October 18, 2025<\/span><\/b>. His fasting TG levels dropped significantly within three days after the treatment, and he was discharged three days post-treatment with no treatment-related adverse events to date.<\/p>\n The principal investigators of the CS-121 IIT are Professor Huan Zhou<\/span><\/b> and Doctor Zhili Wu<\/span><\/b> from the First Affiliated Hospital of Anhui Medical University.<\/p>\n Correctseq, an innovative biotechnology company at the IND clinical stage, previously developed CS-101<\/b>, an ex vivo<\/i> gene-editing therapy that has successfully treated <\/b>dozens of patients with <\/b>\u03b2-thalassemia and sickle cell <\/b>disease<\/b>. The company is advancing the first in vivo<\/i> gene-editing therapy CS-121 toward IND clinical trials and commercialization, aiming to offer “one-<\/b>time treatment, <\/b>lifelong efficacy<\/b>” treatment for patients with chylomicronemia, hypertriglyceridemia, and other metabolic disorders.<\/p>\n Acknowledgments:<\/b> The First Affiliated Hospital of Anhui Medical University, ShanghaiTech University, Shanghai Clinical Research and Trial Center.<\/p>\n About CorrectSequence Therapeutics<\/b> For more information, visit www.correctsequence.com<\/a>.<\/p>\n Media Contact:<\/b> CorrectSequence Therapeutics’ CS-121 Completed Dosing of First Chylomicronemia Patient, Demonstrating Excellent Safety and Significant Efficacy SHANGHAI, Nov. 6, 2025 \/PRNewswire\/ — On November 6, 2025, Shanghai, China, CorrectSequence Therapeutics Co., Ltd. (Correctseq), a clinical-stage biotechnology company pioneering transformer Base Editing (tBE) technology for the treatment of severe diseases, announced that the first patient in its Investigator-Initiated Trial (IIT) of the base-editing therapy CS-121 […]<\/p>\n","protected":false},"author":8,"featured_media":0,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"footnotes":""},"categories":[20],"tags":[],"class_list":["post-41339","post","type-post","status-publish","format-standard","hentry","category-business-news"],"yoast_head":"\n![\"Picture:](\"https:\/\/mma.prnasia.com\/media2\/2815171\/image.jpg?p=medium600\" "\\"Picture:")
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Picture: The world\u2019s first patient of the gene-editing therapy targeting APOC3 (Correctseq\u2019s CS-121) for hyperlipidemia (the 6th from the right) has successfully completed dosing and been discharged.<\/span><\/p>\n<\/p><\/div>\n
CorrectSequence Therapeutics (Correctseq<\/a>), incubated at ShanghaiTech University, is dedicated to leveraging innovative gene-editing technologies to transform the lives of people with severe diseases. The company has developed multiple state-of-the-art base-editing systems that offer exceptional precision, minimize off-target effects, and enhance in vivo <\/i>editing efficiency. Its robust pipeline spans genetic disorders, metabolic diseases, and cardiovascular conditions, with several programs already advancing toward clinical development.<\/p>\n
Business Cooperate: BD@correctsequence.com<\/a>
Clinical Trial Recruitment: CT@correctsequence.com<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"