For decades, the conversation around heart health has centered on cholesterol—specifically LDL, the so-called "bad cholesterol." But while doctors and patients have focused on diet, statins, and newer PCSK9 inhibitors, a hidden genetic risk factor has flown under the radar for approximately 1.4 billion people worldwide 2 8 .
Lp(a) levels are 80-90% genetically determined at birth, making them impervious to diet, exercise, or most conventional medications 8 .
Gene editing promises a fundamentally different approach: a single treatment that provides lifelong protection.
Lp(a) is a liver-derived particle that resembles LDL cholesterol but with a dangerous addition—an extra protein called apolipoprotein(a) 3 . This structural difference makes Lp(a) particularly threatening through two distinct mechanisms.
Promotes the accumulation of plaque in arteries, leading to atherosclerosis and narrowed blood vessels.
Increases the risk of thrombosis by enhancing blood clotting mechanisms 8 .
This dual threat significantly increases the risk of heart attacks and strokes. The genetic nature of Lp(a) creates what cardiologists call "residual cardiovascular risk"—the persistent danger that remains even when all other cholesterol markers appear well-controlled 6 .
Traditional approaches to managing cholesterol rely on chronic medications that require daily pills or regular injections, often over decades. The poor long-term adherence to these regimens—with discontinuation rates reaching 50% within the first year—significantly undermines their real-world effectiveness 6 9 .
| Component | Function | Example in Clinical Development |
|---|---|---|
| Gene Editor | Makes precise changes to DNA sequence | Base editors 1 , CRISPR-Cas9 6 , Novel gene editors 2 4 |
| Guide RNA (gRNA) | Directs the editor to the specific target gene | gRNA targeting LPA gene 5 |
| Delivery Vehicle | Safely transports editing components to liver cells | GalNAc-LNP (lipid nanoparticles) 1 2 |
| Target | Specific gene responsible for disease-related protein | LPA gene (produces apolipoprotein(a)) 3 4 |
While Verve's VERVE-301 program is advancing through preclinical development, recent research from Scribe Therapeutics offers a compelling glimpse into how gene editing could potentially conquer high Lp(a). At the European Society of Cardiology Congress in 2025, the company presented late-breaking data on their experimental therapy STX-1200 5 .
Researchers used transgenic mice engineered with the human LPA gene, creating a pharmacologically relevant model for testing the therapy's effectiveness 5 .
The therapy was administered as a single, very low dose intravenously, allowing it to travel primarily to the liver where Lp(a) is produced 5 .
Once inside liver cells, the CasXE editor and its guide RNA traveled to the nucleus, where they created a permanent modification to the LPA gene designed to reduce production of the problematic apolipoprotein(a) protein 5 .
Researchers conducted comprehensive off-target editing assessments, testing the therapy at supersaturating doses (10X the effective concentration) to identify any unintended genetic changes 5 .
| Parameter | Result | Significance |
|---|---|---|
| Apo(a) Knockdown | >90% reduction | Potentially transforms treatment for millions |
| Dosing Regimen | Single very low dose | One-time treatment approach |
| Off-target Editing | No detectable effects, even at 10X EC90 | Unmatched specificity profile |
| Therapeutic Profile | First preclinical proof-of-concept for CRISPR-based Lp(a) lowering | Establishes new category of genetic medicine |
Our CRISPR therapy is designed to deliver profound and durable Lp(a) lowering for patients worldwide.
STX-1200 achieved >90% reduction in apolipoprotein(a) in preclinical studies 5 .
The work on Lp(a) lowering therapies represents just one front in the broader gene editing revolution for heart disease. Verve Therapeutics has adopted a stepwise approach to clinical development, starting with rare genetic conditions before expanding to broader populations 4 .
| Program | Target Gene | Indications | Development Status |
|---|---|---|---|
| VERVE-102 | PCSK9 | Heterozygous familial hypercholesterolemia (HeFH), ASCVD | Phase 1b clinical trial 1 2 |
| VERVE-201 | ANGPTL3 | Homozygous familial hypercholesterolemia (HoFH), refractory hypercholesterolemia | Phase 1b clinical trial 2 4 |
| VERVE-301 | LPA | ASCVD with high Lp(a) | Preclinical research 2 4 |
The field is gaining significant momentum with:
The development of gene editing therapies for Lp(a) and other lipid risk factors represents a potential paradigm shift from chronic care to one-time cures.
"VERVE-102 holds great promise to transform the care of ASCVD and move that care from daily pills or intermittent injections over decades to a one-dose future for sustained LDL-C lowering."
For millions, cardiovascular risk is written in their genes at birth
Gene editing technologies offer the potential to rewrite this destiny
A single treatment could provide protection against hidden heart risks