CRISPR Lipid-Lowering Race Heats Up as Scribe Seeks $75 Million to Advance Epigenetic Silencing

CRISPR lipid-lowering landscape

On July 2, gene-editing company Scribe Therapeutics filed a registration statement with the U.S. Securities and Exchange Commission (SEC) for a proposed Nasdaq listing under the ticker symbol "SCTX." The company aims to raise up to $75 million, bringing renewed attention to the rapidly evolving CRISPR lipid-lowering field.

Founded in 2017, Scribe Therapeutics is a biotechnology company focused on developing in vivo CRISPR-based gene-editing therapies.

Scribe aims to extend healthy lifespan through disease prevention, beginning with cardiovascular and metabolic disorders. Its lead investigational therapy, STX-1150, uses an epigenetic silencing approach.

Rather than permanently rewriting the DNA sequence, it is designed to durably lower low-density lipoprotein cholesterol (LDL-C)—often called "bad cholesterol"—by suppressing PCSK9 expression.

The therapy has received authorization from Australia's Therapeutic Goods Administration (TGA) to enter a first-in-human trial, with initial data expected in the first half of 2027.

From Chronic Medication to Gene Therapy: A New Model for Lipid Lowering

Cardiovascular disease (CVD) remains the world's leading cause of death. The burden of conditions such as atherosclerotic cardiovascular disease (ASCVD) is closely associated with levels of low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) [Lp(a)], and triglycerides (TG).

For decades, lipid-lowering treatment has relied primarily on ongoing interventions such as statins, PCSK9-targeting antibodies, and small interfering RNA (siRNA) therapies.

As CRISPR gene-editing technologies mature, a growing number of biotechnology companies are exploring one-time treatments that lower blood lipid levels, seeking to shift cardiovascular care from chronic management toward long-term prevention.

The central appeal of CRISPR lies in its potential to deliver long-lasting—and possibly lifelong—benefits after a single treatment.

Target Selection: PCSK9, Lp(a), and ANGPTL3

Conventional lipid-lowering drugs generally work by inhibiting protein function or reducing gene expression. Gene-editing therapies, by contrast, aim to alter the functional state of disease-relevant genes at their source.

The field is currently focused on several targets supported by human genetic evidence:

PCSK9: Individuals with loss-of-function variants in this gene naturally have lower LDL-C levels and a reduced risk of cardiovascular events, making PCSK9 one of the most extensively validated targets.

Lp(a): A highly atherogenic lipoprotein whose levels are largely genetically determined. Approximately one in five people worldwide has elevated Lp(a), and no therapy has yet been approved specifically to reduce Lp(a)-associated cardiovascular risk effectively.

ANGPTL3 and APOC3: Both inhibit triglyceride clearance. Durable inactivation or suppression of these genes is being investigated as a strategy for treating severe hypertriglyceridemia and refractory hypercholesterolemia.

Competition Intensifies in CRISPR Lipid Lowering as Clinical Programs Accelerate

Verve Therapeutics—An Early Mover

Verve Therapeutics has been a major early mover in CRISPR-based lipid lowering. Its candidates VERVE-101 and VERVE-102 use lipid nanoparticle (LNP)-delivered adenine base editing to introduce a single-base change in PCSK9, with the goal of durably inactivating its function.

Early clinical findings indicate that VERVE-102 has been generally well tolerated, with no treatment-related serious adverse events reported. Earlier studies in nonhuman primates showed sustained reductions in PCSK9 protein and LDL-C levels after a single dose, providing proof of concept for one-time lipid-lowering therapy.

CRISPR Therapeutics—A Broad Cardiometabolic Pipeline

Beyond the credibility established by the approved sickle cell disease therapy CASGEVY, CRISPR Therapeutics is advancing three cardiovascular programs:

· CTX310, which targets ANGPTL3, has entered a Phase 1b trial focused on severe hypertriglyceridemia and refractory hypercholesterolemia;

· CTX320, targeting Lp(a), produced reductions of up to 73% during early dose escalation. Enrollment has since been discontinued as the company transitions to the optimized next-generation candidate CTX321;

· The pipeline also includes CTX340, which targets angiotensinogen (AGT) for the treatment of refractory hypertension.

Scribe Therapeutics—A Differentiated Epigenetic Approach

With its newly filed IPO, Scribe Therapeutics is entering the field through a differentiated epigenetic silencing strategy. Unlike the base-editing approaches used by Verve and CRISPR Therapeutics, which alter the DNA sequence, Scribe's ELXR platform combines a catalytically inactive CasX protein with epigenetic effector domains.

The system installs histone modifications and DNA methylation marks at the PCSK9 promoter to silence the gene without cutting or rewriting its DNA sequence—an approach that may, in principle, offer a degree of reversibility.

The discovery and validation of key targets such as PCSK9 and ANGPTL3 depend on precise gene-edited models that support mechanistic research, drug screening, and efficacy evaluation.

Powered by its proprietary EditX™ gene-editing platform and an optimized CRISPR/Cas9 system, EDITGENE provides custom gene-edited cell model development services across a broad range of disease-relevant targets. These models support functional studies, drug screening, and mechanism-of-action validation for metabolic targets including PCSK9.

References

[1] Renaissance Capital. Cardiovascular diseases biotech Scribe Therapeutics files for a $75 million IPO. 2026.

[2] Scribe Therapeutics. Scribe Therapeutics Presents Late-Breaking Preclinical Data Supporting STX-1150, a Clinical-Stage Epigenetic Silencing Therapy Designed to Achieve Years of LDL-C Lowering After a Single Dose. Scribe Therapeutics Official Website.

[3] CRISPR Therapeutics. Pipeline: Cardiovascular and Metabolic Disease Programs. CRISPR Therapeutics Official Website.

[4] Verve Therapeutics. In Vivo Base Editing Programs for Cardiovascular Disease. Verve Therapeutics Official Website.