The Future of Medical Revolution: New Technology Dramatically Lowers Cholesterol with Gene Editing

The Future of Medical Revolution: New Technology Dramatically Lowers Cholesterol with Gene Editing

2025年11月10日 08:41

Introduction: Key Points of the News

CRISPR Therapeutics in the US conducted a Phase I/first-in-human clinical trial, where a primary treatment (candidate name: CTX310) using CRISPR-Cas9 to turn off the ANGPTL3 gene in liver cells reportedly reduced LDL cholesterol and triglycerides by about half. The results were presented at the American Heart Association (AHA) 2025 Annual Scientific Sessions and published on the same day in the New England Journal of Medicine (NEJM). The trial involved 15 participants in a small-scale, early-stage study primarily aimed at safety and dose exploration, but it has garnered attention as a demonstration towards the vision of "lifetime lipid reduction with a single gene edit."American Heart Association


What's New: "One and Done" Targeting ANGPTL3

This approach aims to knock out ANGPTL3, which is involved in lipid metabolism in the liver, employing a "chasing two rabbits" strategy to lower both LDL-C and triglycerides. mRNA (Cas9) and guide RNA are delivered to liver cells via LNP (lipid nanoparticles), executing the gene "scissors" with a single intravenous infusion. In the high-dose group, both indicators were reduced by about 50%. It was administered in addition to existing treatments (such as statins), and a deep reduction was maintained during the observation period.New England Journal of Medicine


ANGPTL3 emerged as a target from observations of people with familial functional decline, as a "natural experiment" gene that could reduce atherosclerosis risk, and has been targeted by other means such as RNAi. Gene editing is characterized by aiming for long-term effects with a single modification.Nature


Interpreting the Data: Limitations Due to Small Scale and Still Significant Impact

  • Trial Scale: N=15. The aim was safety and dose exploration.New England Journal of Medicine

  • Effect Size: Approximately 50% reduction in both LDL-C/triglycerides with high dose. The effect was confirmed for at least 60 days.WIRED

  • Safety: No serious treatment-related adverse events reported. A patient with a history of severe coronary artery disease suddenly died 6 months after low-dose administration, but it was considered unlikely to be treatment-related. Long-term follow-up and larger-scale verification are essential.New England Journal of Medicine

The above is sufficiently newsworthy as the **"first step of evidence." Particularly, the direction of targeting common diseases (dyslipidemia) with gene editing marks a tectonic shift from previous successes focused on rare diseases. However, there are many **uncertain elements such as long-term efficacy and safety, off-target editing, and immune reactions.New England Journal of Medicine


Competition & Comparison: Relationship with Base Editing Targeting PCSK9

A venture (Verve Therapeutics) targeting PCSK9 with base editing showed LDL reduction in early trials, but was forced to revise protocols and redesign particles due to signals of thrombocytopenia and liver damage. **The differences in targets (ANGPTL3 vs. PCSK9) and editing methods (Cas9 cutting vs. base editing)** will be the focus of future comparisons of safety profiles and modes of effect.BioPharma Dive


Background Concerns: Death in Another CRISPR Trial

Another company, Intellia Therapeutics, in a late-stage trial targeting ATTR amyloidosis, had a patient who developed severe liver damage after administration and was hospitalized in late October, subsequently dying in early November. The company has halted administration and screening and is working with regulatory authorities. While complex factors such as disease state and age are suggested, market and medical community caution towards the overall picture of CRISPR has undoubtedly increased. Coupled with the fact that the ANGPTL3 trial remains small-scale and short-term in terms of safety, the sentiment that **"hasty expansion is forbidden"** prevails.Reuters


SNS Reactions: Balance of Enthusiasm and Caution

Experts, academic societies, and investor accounts reacted in succession during the AHA session. To summarize the impressive points:

  • Specialized Journal/JACC: "First human CRISPR cardiovascular trial showed safety and LDL/TG reduction," reported as breaking news. A tone of "cautious optimism" is visible in major academic media.X (formerly Twitter)

  • RNA Medicine Analyst: Mentioned the possibility of strong LDL reduction relative to ANGPTL3 reduction, showing interest in mechanism differences.X (formerly Twitter)

  • European Atherosclerosis Society (EAS): Emphasized the point of robust lipid reduction with a single administration. A reception mindful of clinical application prospects.X (formerly Twitter)

  • Corporate Official/CRISPRTX: Highlighted the **late-breaking news** selection at AHA.X (formerly Twitter)

  • Investor Circles ($CRSP): Coexistence of "Biology becomes programmable"-type technological optimism and realistic caution regarding regulation and long-term safety.X (formerly Twitter)

  • Clinician Threads: Envisions the next chapter of lipid management where CRISPR/siRNA/antibodies coexist.X (formerly Twitter)

The excitement on SNS is real, but it's also important that both positive and negative **"rational concerns"** are being visualized. Scaling up from rare diseases to common diseases faces complex hurdles in healthcare economics, ethics, and regulation

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What This Means: The Wall of Treatment Adherence and Healthcare Economics

Compared to treatments like statins or PCSK9 antibodies/siRNA that require continuous administration, a "one-time" treatment could overcome the adherence barrier. However, prices tend to be high, and payment models (installment, outcome-based) and uncertainty of long-term safety will be key to insurance coverage. Even if rare, off-target editing and immune response are irreversible, demanding more risk and accountability than conventional drugs.


Next Milestone: Who, When, and How to Expand

The Washington Post reports that the research lead estimates a transition to **"late-stage trials in about a year." However, this is a positive estimate** and there is significant uncertainty regarding regulatory decisions, the impact of the Intellia case, and dose optimization. Starting with **narrowing down the target population (familial hypercholesterolemia or very high-risk groups)**, the issue over a span of several to a dozen years will be whether it can be expanded to general primary prevention.The Washington Post


Editorial Comments: Balancing Expectations and Caution

  • Science: The results this time realistically suggest a paradigm shift from reversible pharmacology to irreversible genomic medicine.

  • Ethics: Expansion to young and primary prevention##

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