Can a one-time gene edit replace lifelong cholesterol drugs? Experts weigh early LDL breakthrough

A new experimental gene-editing therapy aimed at lowering “bad” cholesterol has sparked global scientific interest after early clinical trial results showed substantial and potentially long-lasting reductions in low-density lipoprotein (LDL) levels, one of the most important risk factors for heart attacks and strokes.

Developed using CRISPR-based base-editing technology, the treatment targets the PCSK9 gene, which plays a central role in regulating how the body clears LDL cholesterol from the bloodstream. Early data from Eli Lilly’s VERVE-102 programme suggests that a single infusion could reduce LDL levels by as much as 62%, with effects persisting for up to 18 months in some patients studied so far.

If confirmed in larger trials, the approach could represent a major shift in cardiovascular medicine, moving from lifelong cholesterol-lowering drugs to a one-time genetic intervention that modifies disease biology at its source.

A shift from lifelong treatment to genetic correction

For decades, high cholesterol has been managed through statins, ezetimibe and injectable PCSK9 inhibitors — all of which require long-term or repeated dosing. While highly effective, these therapies depend heavily on sustained patient adherence.

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Experts say gene editing introduces a fundamentally different concept: durable biological correction.

“For years, we have relied on lifelong medications to control LDL cholesterol,” said Dr Shrinidhi Nathany, Consultant, Molecular Hematology & Oncology, Fortis Hospital (Gurugram). “Now we are exploring whether a one-time intervention could replicate naturally protective genetic states seen in some individuals.”

He said that the therapy uses base editing, a refined version of CRISPR technology to make precise changes to DNA without cutting both strands. Unlike earlier CRISPR methods that act like “molecular scissors,” base editing works more like correcting a single letter in a genetic code, reducing the likelihood of structural DNA damage.

By switching off PCSK9 production in liver cells, the therapy enhances the body’s ability to remove LDL cholesterol more efficiently.

Comparable to or stronger than existing therapies

Cardiologists say the early results are particularly striking because of the magnitude of LDL reduction achieved with a single dose.

“This is one of the most exciting developments in preventive cardiology in recent years,” said Dr Sai Sudhakar, Chief Interventional Cardiologist and Chief Cardiac Transplant Physician, Gleneagles Hospital (Fortis network).

He said that LDL cholesterol is a key modifiable driver of atherosclerosis, the process that leads to blocked arteries and heart attacks.

“Traditional statins typically reduce LDL by 20% to 50%, while injectable PCSK9 inhibitors achieve around 50% to 60%. The early gene-editing results appear comparable, and in some cases even superior but with the advantage of a single treatment rather than lifelong dosing,” he said.

The PCSK9 pathway itself is already validated through existing drugs, which makes it an attractive target for more permanent genetic approaches.

Promise, but with scientific caution

Despite the enthusiasm, experts stress that the therapy remains experimental and must be interpreted cautiously.

“This is still early-stage research with limited patient numbers,” Dr Sudhakar said. “While the efficacy signals are encouraging, long-term safety data is essential before considering widespread use.”

A key concern is the permanence of gene editing. Because the therapy creates lasting changes in DNA, any unintended effects could also persist.

Safety, ethics and long-term uncertainty

One of the central scientific concerns is the possibility of off-target effects, where genetic edits occur in unintended regions of the genome.

“Even with modern base-editing systems designed for high precision, no gene-editing tool is completely risk-free,” said Dr Niti Raizada, Principal Director – Medical Oncology & Hemato-Oncology, Fortis Hospitals, (Bengaluru). “Unintended changes could have consequences that only become visible years later.”

She added that long-term monitoring will be critical before such therapies can move from experimental trials to routine clinical use.

Dr Nathany also said that researchers are increasingly using advanced computational modelling and deep genomic sequencing to minimise risks, but stressed that caution remains essential given the permanence of genetic interventions.

Implications for India and beyond

Experts believe the potential impact could be particularly significant in countries like India, where cardiovascular disease is a leading cause of premature death and many patients struggle with long-term medication adherence.

However, challenges remain around cost, access and healthcare infrastructure, especially in the early stages of deployment.

“Initially, such therapies will be expensive and limited to specialised centres,” Dr Sudhakar said. “But over time, if outcomes remain strong, they could become a valuable addition to preventive cardiology.”

A glimpse of future medicine

While researchers warn that gene editing will not replace existing therapies anytime soon, many see it as part of a broader transformation in medicine, one that shifts focus from lifelong disease management to targeted, durable interventions.

“Genetic medicine may become a major pillar of future healthcare,” Dr Nathany said. “But it will likely complement, not replace, lifestyle changes and preventive care.”

For now, the findings offer a glimpse into a future where controlling cholesterol and potentially other chronic diseases, may no longer depend on daily pills, but on precise genetic correction delivered once in a lifetime.