Imagine receiving a single medical treatment that could keep your cholesterol under control for decades, potentially eliminating the need for daily medication and fundamentally altering how modern medicine approaches chronic illness. Advances in gene editing are bringing that possibility closer to reality, moving science closer to therapies that function like software updates for human biology. But medical experts emphasize that the very technology capable of revolutionizing healthcare also raises profound questions regarding safety, permanent genetic changes, and unintended consequences that may take decades to fully understand.
Gene therapy is already being utilized to treat certain serious and debilitating illnesses. These advanced treatments can introduce working copies of genes, silence harmful genetic activity, or make precise, targeted modifications directly to human DNA. Unlike conventional pharmaceuticals that must be taken repeatedly—often daily—to maintain their therapeutic effects, some genetic treatments are intentionally designed to work after just a single administration.
More than 6,000 rare genetic disorders have been identified by medical researchers, although only a small proportion currently possess specific genetic targets that can be successfully treated. Even so, gene therapies have already achieved critical medical successes against severe conditions such as spinal muscular atrophy and sickle cell disease, offering new hope to patients who previously had few or no viable options.
Now, researchers are aggressively exploring whether similar genomic approaches could help prevent or manage far more widespread health problems, including high cholesterol, heart disease, obesity, and diabetes.
That expansion of purpose raises a fundamental bioethical and clinical question: Just because scientists possess the technical capability to 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, researchers, and policymakers must carefully weigh the potential benefits of genomic therapies against their very real risks.
The two gene therapy researchers explain why these innovative treatments are uniquely promising, what differentiates them fundamentally from conventional medicines, and what critical milestones must be achieved 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 tantalizing possibility of achieving lasting, long-term health results without the burden of repeated treatments or chronic disease management.
Traditional medicines generally work only as long as patients continue taking them, meaning that missing a dose or stopping treatment can cause a condition to return or worsen. Genomic therapies operate on an entirely different level because they act directly upon the body’s fundamental genetic material. They may provide a healthy version of a gene, suppress a gene responsible for harmful biological effects, or modify a specific DNA sequence to correct an underlying fault.
This mechanism makes it possible to develop treatments intended to work effectively after a single dose. Such therapies are frequently referred to in the medical community as "one-and-done" treatments.
However, receiving a treatment only once does not necessarily mean its biological effects will remain uncomplicated for a lifetime, nor does it guarantee that the treatment can be repeated if initial results begin to fade.
Smith explains that many modern gene therapies rely on modified, harmless viruses to carry genetic instructions safely into human cells. Because these delivery vehicles are derived from viruses, the human immune system can recognize them and develop an aggressive immune response against them. As a result, administering the exact same gene therapy treatment a second time may prove difficult or entirely impossible, even if its clinical benefits begin to wane over the years.
Another crucial distinction concerns which types of cells are altered during the procedure. Current clinical gene therapies generally target somatic cells, which comprise the body’s normal tissues and organs other than those involved in human reproduction. Unlike controversial germline editing, these somatic treatments are strictly designed not to create genetic changes that can be inherited by future generations, limiting the scope of the modification to the living patient.
Why Gene Editing Common Diseases Raises New Risks
For individuals living with rare, devastating genetic conditions, the potential benefits of gene therapy may clearly and decisively outweigh the potential dangers. Some patients suffering from these conditions have few, if any, effective treatment options available, making even an experimental and permanent intervention well worth considering.
The clinical situation becomes considerably more complicated, however, when the exact same gene-editing technology is deployed against common, widespread diseases.
Conditions such as high cholesterol, heart disease, obesity, and type 2 diabetes already possess established, conventional treatments. Many of these standard medications can be easily adjusted as a patient’s health condition changes over time, or discontinued entirely if troublesome side effects or adverse reactions develop.
A permanent genetic intervention, by its very nature, may not offer that same level of clinical flexibility. Once a DNA sequence is altered or a gene is permanently silenced, turning back the clock is exceptionally difficult with current technology.
Murthy also points to a major public health concern involving the sheer scale of the patient population that might eventually receive these treatments. Even a serious side effect that occurs only rarely during clinical trials could still harm a substantial number of individual patients if a genomic therapy is eventually administered to millions of people worldwide.
For that reason, medical treatments intended for widespread, mass use must meet exceptionally demanding safety standards before they are cleared for the general public.
Evaluating the Long-Term Unknowns
To help determine when and how genomic therapy is truly appropriate, Smith and Murthy propose evaluating several essential factors, keeping a sharp focus on the long-term realities of permanent medical interventions.
Evaluating these factors is particularly challenging because of the limitations inherent in traditional clinical trial designs. Clinical trials typically involve relatively small groups of carefully selected patients who are monitored for limited periods, often spanning just a few months or several years. Although these initial studies can identify many important acute safety concerns, they may easily miss extremely rare complications or chronic problems that take years or even decades to develop.
Some adverse biological effects might only become fully apparent after a novel treatment has reached a much larger, more diverse population in the real world.
Smith argues that rigorous long-term monitoring cannot simply be treated as an afterthought in the drug development pipeline. Instead, it needs to be established as an essential, non-negotiable part of how gene therapies are integrated into standard medical practice.
Patient registries, which systematically collect health information about individuals receiving particular specialized treatments, have already demonstrated how valuable extended follow-up can be in detecting signals of trouble.
However, advanced therapies that could eventually reach millions of patients will require large-scale monitoring systems capable of operating efficiently across entire healthcare infrastructures.
These tracking systems must be completely independent and standardized so that independent researchers can consistently evaluate whether treatments remain clinically effective and whether unexpected health problems or late-onset side effects appear over time.
Without reliable long-term data, doctors may struggle to determine the full consequences of genetic interventions that cannot easily be reversed or modified.
Could Some Genetic Changes Be Too Risky to Make Permanent?
Another profound concern among bioethicists and clinicians is whether certain diseases or complex biological processes are suitable for permanent treatment at all.
Murthy emphasizes that developing the technical ability to alter a specific genetic target does not automatically make doing so the best or safest medical decision for a patient.
Some chronic conditions require careful, continuous adjustments to medication doses over time as a person ages or their metabolic state shifts. In other cases, the physiological margin between an effective medical treatment and a harmful one can be extremely narrow. Altering a biological process either too much or too little through permanent editing could create severe, unforeseen physiological complications.
Conventional medications offer an important clinical advantage in these situations because doctors retain the ability to modify, reduce, or stop treatment immediately as needed.
Permanent gene therapies generally lack that vital option once administered.
Scientists may eventually overcome this technological limitation by developing advanced genetic treatments with built-in biological "off-switches," inducible promoters, or other innovative methods for safely reversing their effects if complications arise.
Until those advanced safety approaches have been proven to work reliably in humans, the ability to easily undo or adjust a treatment remains a major safety advantage of traditional, non-permanent medicine.
The Financial Challenge Facing Mainstream Gene Therapy
Safety is not the only formidable barrier standing in the way of bringing advanced gene editing into mainstream healthcare. The question of cost could ultimately determine whether these breakthrough treatments become widely available to the general public or remain exclusive interventions.
Some existing gene therapies currently carry list prices exceeding $1 million for a single patient, with several advanced treatments costing substantially more.
Such staggering price tags may be considered justifiable by healthcare systems and insurers for certain rare, life-threatening conditions, particularly when alternative treatment options are extremely limited or nonexistent.
However, applying similar multi-million-dollar pricing models to chronic diseases affecting tens of millions of people would place enormous, unsustainable financial pressure on national healthcare systems and insurance providers alike.
Smith and Murthy argue that long-term affordability and equitable access must therefore be part of the scientific and economic discussion from the very beginning of the development process.
Even a remarkably effective gene therapy could inadvertently create severe new healthcare inequalities if only a tiny percentage of affluent patients could actually obtain it. Researchers, healthcare providers, and policymakers must consider not just whether these sophisticated treatments work biologically, but also whether they can be delivered broadly without worsening existing socioeconomic health disparities.
Looking Toward the Future of Cardiovascular Care
Despite these substantial scientific, safety, and economic challenges, the possibility of using gene editing to prevent common chronic diseases is becoming increasingly realistic as laboratory research progresses.
Researchers are already conducting early-stage clinical studies to investigate whether a single genetic treatment can produce safe, long-lasting reductions in low-density lipoprotein (LDL), commonly referred to as "bad" cholesterol.
LDL cholesterol is a primary driver in the progressive buildup of fatty deposits inside arterial walls, a process that significantly increases the risk of heart attacks, strokes, and other serious cardiovascular events. Lowering LDL levels over extended periods is a cornerstone strategy for reducing long-term cardiovascular risk in at-risk populations.
If gene editing can safely produce sustained reductions in bad cholesterol, it could eventually offer an entirely new paradigm for protecting cardiovascular health without requiring patients to adhere to lifelong medication regimens.
However, promising early results alone will not be enough to justify widespread clinical adoption.
Before these therapies become routine medical options for common conditions, researchers will need convincing, long-term evidence that their therapeutic benefits last, their risks remain acceptably low over many years, and their economic costs are manageable. Reliable safeguards and monitoring networks will also be essential.
For Smith and Murthy, the primary objective is not to hold back the progress of genetic medicine. Rather, it is to ensure that a technology with the extraordinary potential to transform modern healthcare is introduced carefully, ethically, and responsibly.
As gene therapy officially moves beyond rare disorders toward chronic conditions affecting millions of people, the central challenge for the medical community will be ensuring that the bright promise of lasting protection does not come at the expense of long-term patient safety.