For millions of people, managing high cholesterol means a lifetime of daily pills, frequent injections, and strict diets. But what if a single treatment could permanently protect your heart?
This isn't science fiction—it's the promise of gene editing therapy, a revolutionary approach that could transform cardiovascular medicine from chronic management to a one-time cure 3 .
At the forefront of this revolution is Verve Therapeutics, pioneering treatments that target the very genes responsible for cholesterol production. Their most ambitious project aims to tackle lipoprotein(a), or Lp(a)—a "sticky," genetically determined cholesterol particle that conventional medications can't control 1 5 . With recent major pharmaceutical partnerships and stunning clinical trial results, the future of heart disease prevention is being rewritten right now.
Lipoprotein(a), pronounced "LP little a," is a cholesterol particle often called the "silent killer" of cardiovascular health.
Lp(a) levels are 70-90% genetically determined from birth, making them unresponsive to lifestyle changes 1 .
Like the more familiar LDL cholesterol (often called "bad cholesterol"), Lp(a) contributes to plaque buildup in arteries 1 . However, Lp(a) has a crucial difference: it contains an additional protein called apolipoprotein(a) that makes it particularly dangerous 1 5 .
This extra protein prevents the body's natural clearing mechanisms from removing Lp(a) from the bloodstream, giving it an exceptionally long half-life and making it exceptionally effective at creating blockages 1 . Elevated Lp(a) levels are an established risk factor for atherosclerotic cardiovascular disease, ischemic stroke, thrombosis, and aortic stenosis 1 5 .
Genetically determined Lp(a) levels
People worldwide with elevated Lp(a)
Response to statins and lifestyle changes
"This is like a genetic disease," says Sekar Kathiresan, co-founder and CEO of Verve Therapeutics 1 .
Gene editing technologies have evolved dramatically in recent years. While most people have heard of CRISPR—the "genetic scissors" that can cut and edit DNA—researchers have developed even more precise tools 6 8 .
The latest advancement is base editing, which works like a genetic spell-checker 2 . Instead of cutting the DNA double-helix, base editors make single-letter changes in the genetic code—changing an A to a G, for instance—with remarkable precision and potentially greater safety 8 .
The editing technology itself is only half the challenge—it also needs to be delivered to the correct cells in the body. Verve's therapies use GalNAc-LNP delivery technology, specialized lipid nanoparticles that act like homing devices for liver cells 2 4 . Since the liver is the control center for cholesterol production, this delivery system ensures the gene editor reaches precisely where it needs to work.
| Component | Function | Example in Verve's Therapies |
|---|---|---|
| Base Editor mRNA | Blueprint for creating the base editing protein inside cells | mRNA encoding adenine base editor (ABE) 2 |
| Guide RNA (gRNA) | Molecular GPS that directs the editor to the target gene | gRNA targeting PCSK9 or LPA gene 2 |
| Delivery Nanoparticles | Protective vessels that transport editing components to target cells | GalNAc-LNP for liver-specific delivery 4 |
| Target Gene | Specific DNA sequence to be edited | PCSK9, ANGPTL3, or LPA genes 2 4 |
The first human trial of Verve's gene editing approach, reported in November 2023, produced stunning results 3 . The study involved nine participants with heterozygous familial hypercholesterolemia—an inherited condition causing extremely high cholesterol levels and heart attack risk at an early age 3 .
Participants received a single infusion of VERVE-101, designed to permanently disable the PCSK9 gene in the liver. This gene regulates LDL cholesterol by controlling how many cholesterol-clearing receptors appear on liver cells 3 .
| Dose Level | LDL Cholesterol Reduction | PCSK9 Protein Reduction |
|---|---|---|
| 0.45 mg/kg | 39% and 48% in two participants | 47% and 59% |
| 0.6 mg/kg | 55% in one participant | 84% |
Source: American Heart Association Scientific Sessions 2023 3
"Instead of daily pills or intermittent injections over decades to lower bad cholesterol, this study reveals the potential for a new treatment option—a single-course therapy that may lead to deep LDL-C lowering for decades," said Dr. Andrew M. Bellinger, the study's senior author 3 .
Building on this success, Verve introduced VERVE-102, an enhanced version using base editing technology 2 . The Heart-2 Phase 1b clinical trial results announced in April 2025 showed even more impressive outcomes:
| Dose Cohort | Mean LDL-C Reduction | Maximum LDL-C Reduction |
|---|---|---|
| 0.3 mg/kg | 21% | Not specified |
| 0.45 mg/kg | 41% | Not specified |
| 0.6 mg/kg | 53% | 69% |
Source: Verve Therapeutics Q1 2025 Report 4
The trial also demonstrated an excellent safety profile, with no treatment-related serious adverse events—addressing early concerns about the technology's safety 4 .
In June 2023, Verve announced a landmark partnership with pharmaceutical giant Eli Lilly to develop a gene editing therapy specifically for Lp(a) 1 . The deal included $60 million in upfront payments and up to $465 million in milestone payments 1 . This partnership has since deepened, with Lilly ultimately acquiring Verve in a deal worth up to $1.3 billion .
The collaboration aims to develop VERVE-301, a novel gene editing medicine designed to permanently turn off the LPA gene in the liver, directly targeting the source of elevated Lp(a) 4 .
VERVE-301 uses the same proven delivery system as Verve's other treatments but targets a different gene. The LPA gene provides instructions for making the apolipoprotein(a) portion of Lp(a) 1 5 . By permanently disabling this gene, VERVE-301 aims to reduce Lp(a) production at its source, potentially providing lifelong protection from its dangerous effects.
Verve received a milestone payment from Lilly in the first quarter of 2025 when VERVE-301 was nominated as the development candidate, indicating promising preclinical results 4 . While human trials haven't yet begun, the established success of Verve's platform against PCSK9 suggests strong potential for the Lp(a)-targeting approach.
The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to VERVE-102, a regulatory pathway designed to accelerate the development of treatments for serious conditions with unmet medical needs 4 .
Any permanent genetic treatment rightly raises safety concerns. The early trials have shown encouraging safety profiles, with the majority of adverse events being mild and unrelated to treatment 3 4 . Serious cardiovascular events that did occur were in patients with pre-existing advanced coronary artery disease and were not deemed related to the treatment itself 3 .
Regulatory agencies require extended follow-up for all gene therapy participants—typically 15 years—to monitor for long-term effects 3 . This careful oversight ensures that any potential risks are identified and understood.
Verve is pursuing a stepwise approach to development, initially treating patients with the highest cardiovascular risk before potentially expanding to broader populations 2 4 . The company plans to initiate a Phase 2 clinical trial for VERVE-102 in the second half of 2025 and expects to provide updates on its Lp(a) program in the same timeframe 4 .
Gene editing for cholesterol represents a paradigm shift from chronic management to permanent correction. What was once science fiction is now clinical reality: a single treatment that can permanently alter cholesterol genes and provide lifelong protection against heart disease.
As Dr. Sekar Kathiresan, CEO of Verve Therapeutics, envisions, this technology could "fundamentally transform the journey for patients living with cardiovascular disease from decades of chronic care to a one dose future" 4 .
While more research is needed and these treatments are not yet widely available, the impressive clinical results to date suggest that the era of one-time, permanent solutions for genetic heart disease risks is dawning. For the billions of people worldwide living with elevated Lp(a) and other inherited cholesterol disorders, this scientific revolution offers hope for a future free from the shadow of cardiovascular disease.
Potential to replace lifelong medications with a single therapy
Targets the root cause of genetically determined high cholesterol
Potential to significantly reduce cardiovascular events