Gene editing could replace a lifetime of medication, but there’s a catch

Gene therapy is already being used to treat certain serious illnesses. These treatments can introduce working copies of genes, silence harmful genetic activity, or make changes directly to DNA. Unlike conventional medications that must be taken repeatedly, some genetic treatments are designed to work after just one administration.

More than 6,000 rare genetic disorders have been identified, although only a small proportion currently have targets that can be treated. Gene therapies have already achieved important successes against conditions such as spinal muscular atrophy and sickle cell disease.

Now, researchers are exploring whether similar approaches could help prevent or manage far more widespread health problems, including high cholesterol, heart disease, obesity, and diabetes.

That raises a fundamental question: Just because scientists can permanently change a person’s genetic activity, does that mean they should?

In a perspective published in JAMA Internal Medicine, University of Michigan Health Frankel Cardiovascular Center cardiologists Eric D. Smith, M.D., and Venkatesh L. Murthy, M.D., Ph.D., outline how doctors and researchers should weigh the potential benefits of genomic therapies against their risks.

The two gene therapy researchers explain why these treatments are so promising, what makes them different from conventional medicines, and what must happen before they can be safely offered to millions of people.

Why One-Time Gene Therapy Is Different From Daily Medication

One of the most appealing features of gene therapy is the possibility of achieving lasting results without repeated treatments.

Traditional medicines generally work only as long as patients continue taking them. Genomic therapies operate differently because they act on genetic material itself. They may provide a healthy version of a gene, suppress a gene responsible for harmful effects, or modify a specific DNA sequence.

This makes it possible to develop treatments intended to work after a single dose. Such therapies are often called “one-and-done” treatments.

However, receiving a treatment only once does not necessarily mean its effects will last a lifetime.

Smith explains that many gene therapies use modified viruses to carry genetic instructions into cells. The immune system can recognize these delivery vehicles and develop a response against them. As a result, administering the same treatment again may be difficult or impossible, even if its benefits begin to fade.

Another important distinction concerns which cells are changed. Current gene therapies generally target somatic cells, which are the body’s cells other than those involved in reproduction. Unlike germline editing, these treatments are not intended to create genetic changes that can be inherited by future generations.

Why Gene Editing Common Diseases Raises New Risks

For people living with rare, devastating genetic conditions, the benefits of gene therapy may clearly outweigh the potential dangers. Some patients have few effective treatment options, making even an experimental intervention worth considering.

The situation becomes considerably more complicated when the same technology is used against common diseases.

Conditions such as high cholesterol, heart disease, obesity, and diabetes already have established treatments. Many of these medications can be adjusted as a patient’s condition changes or discontinued if troublesome side effects develop.

A permanent genetic intervention may not offer that flexibility.

Murthy also points to a major concern involving the number of people who might eventually receive these treatments. A serious side effect that occurs only rarely could still harm a substantial number of patients if a therapy is administered to millions.

For that reason, treatments intended for widespread use must meet especially demanding safety standards.

Five Questions Scientists Say Must Be Answered

To help determine when genomic therapy is appropriate, Smith and Murthy propose evaluating five essential factors:

1. Disease severity: How serious is the condition being treated, and how much could patients benefit?
2. Existing treatments: Are there already effective therapies that can be adjusted or discontinued if necessary?
3. Treatment durability: Is the targeted tissue suitable for an intervention intended to produce lasting results after one dose?
4. Delivery risks: Are the potential dangers associated with delivering the genetic treatment reasonable given the severity of the disease?
5. Long-term monitoring: Can researchers reliably track safety and effectiveness over many years, particularly when large numbers of people receive the treatment?

The final question may be especially challenging.

Clinical trials typically involve relatively small groups of patients who are monitored for limited periods. Although these studies can identify many important safety concerns, they may miss extremely rare complications or problems that take years to develop.

Some adverse effects might only become apparent after a treatment has reached a much larger population.

The Problem of Tracking Risks That Could Emerge Years Later

Smith argues that long-term monitoring cannot be treated as an afterthought. It needs to be an essential part of how gene therapies are introduced into medical practice.

Patient registries, which collect information about people receiving particular treatments, have already shown how valuable extended follow-up can be.

However, therapies that could eventually reach millions of patients will require monitoring systems capable of operating on a much larger scale.

These systems must be independent and standardized so researchers can consistently evaluate whether treatments remain effective and whether unexpected health problems appear over time.

Without reliable long-term data, doctors may struggle to determine the full consequences of genetic interventions that cannot easily be reversed.

Could Some Genetic Changes Be Too Risky to Make Permanent?

Another concern is whether certain diseases or biological processes are suitable for permanent treatment at all.

Murthy emphasizes that developing the ability to alter a genetic target does not automatically make doing so the best medical decision.

Some conditions require careful adjustments to medication doses over time. In other cases, the difference between an effective treatment and a harmful one can be extremely small. Changing a biological process too much or too little could create serious complications.

Conventional medications offer an important advantage in these situations because doctors can modify or stop treatment as needed.

Permanent gene therapies generally lack that option.

Scientists may eventually overcome this limitation by developing genetic treatments with built-in biological “off-switches” or other methods for reversing their effects.

Until those approaches have been shown to work reliably, the ability to undo or adjust a treatment remains an important safety advantage of traditional medicine.

The Million-Dollar Challenge Facing Gene Therapy

Safety is not the only barrier to bringing gene editing into mainstream healthcare. Cost could also determine whether these treatments become widely available.

Some existing gene therapies have list prices above $1 million for a single patient, and several cost substantially more.

Such prices may be considered justifiable for certain rare, life-threatening conditions, particularly when treatment options are extremely limited.

But applying similar pricing to diseases affecting millions of people would place enormous financial pressure on healthcare systems.

Smith and Murthy argue that affordability and access must therefore be part of the discussion from the beginning.

Even a highly effective gene therapy could create new healthcare inequalities if only a small percentage of patients could obtain it. Researchers and policymakers must consider not just whether these treatments work, but also whether they can be delivered without making existing disparities worse.

Could One Gene-Editing Treatment Prevent Heart Disease for Decades?

Despite these challenges, the possibility of using gene editing to prevent common diseases is becoming increasingly realistic.

Researchers are already conducting early studies to investigate whether a single genetic treatment can produce long-lasting reductions in LDL, commonly known as “bad,” cholesterol.

LDL cholesterol contributes to the buildup of fatty deposits inside arteries, which can increase the risk of heart attacks and other cardiovascular problems. Lowering LDL over extended periods is an important strategy for reducing cardiovascular risk.

If gene editing can safely produce sustained reductions, it could eventually offer a new approach to protecting cardiovascular health without requiring patients to take medication indefinitely.

However, promising early results will not be enough to justify widespread use.

Before these therapies become routine options for common conditions, researchers will need convincing evidence that their benefits last, their risks remain acceptably low over many years, and their costs are manageable. Reliable safeguards will also be essential.

For Smith and Murthy, the objective is not to hold back genetic medicine. It is to make sure that a technology with the potential to transform healthcare is introduced carefully and responsibly.

As gene therapy moves beyond rare disorders toward conditions affecting millions of people, the central challenge will be ensuring that the promise of lasting protection does not come at the expense of long-term patient safety.