The technical backdrop to their argument is a field advancing on multiple fronts simultaneously. A review by Pan and colleagues, published in the same journal, traces how CRISPR-Cas9 and its increasingly refined descendants, including base editing, prime editing, and AI-guided RNA design, are converging with cell and vector engineering to offer potentially curative options for children with rare monogenic diseases. Base editing chemically converts one DNA letter into another without cutting both strands of the double helix, while prime editing allows more precise insertions and deletions with fewer unwanted byproducts. Machine learning tools are accelerating the design of RNA molecules and delivery vehicles, shortening development timelines that once stretched over decades.

The clinical results are no longer theoretical. Several gene therapy products now carry approval from the Food and Drug Administration or the European Medicines Agency for pediatric indications, and dozens more sit in active clinical trials. Diseases once uniformly fatal or progressively disabling, such as spinal muscular atrophy and metachromatic leukodystrophy, now have potentially curative options. The commentary describes this as an inflection point, but one whose promise is fragile, because access for children today and development of new therapies tomorrow hinge on coverage decisions made in insurance boardrooms as much as in laboratories.

Price is the most visible obstacle. Atidarsagene autotemcel, marketed as Lenmeldy, is a one-time therapy for metachromatic leukodystrophy with a list price of 4.25 million dollars, making it among the most expensive medicines ever approved. Onasemnogene abeparvovec, sold as Zolgensma, is a single infusion for spinal muscular atrophy priced near 2.1 million dollars. Exagamglogene autotemcel, known as Casgevy, the first CRISPR-edited cell therapy approved for sickle cell disease, and lovotibeglogene autotemcel, or Lyfgenia, a lentiviral-edited counterpart, list in a similar range. These figures dwarf the cost of conventional orphan drugs and raise immediate questions about affordability for health plans serving children.

Yet the authors caution against reading these prices as simple profiteering. The costs reflect the genuine expense of manufacturing an individualized cell or gene product, a process that involves harvesting a patient’s own cells, engineering them in specialized facilities, performing quality control, and returning them to the patient, all under regulatory scrutiny. Independent health economic assessments have judged several of these therapies cost-effective when measured against the lifetime value of a one-time cure compared with years or decades of standard care, which for conditions like sickle cell disease includes repeated hospitalizations, transfusions, and pain crises. From that perspective, a multimillion-dollar price tag can represent a bargain over a lifetime, even as it creates an acute budget shock for any single insurer.

This tension between long-term value and short-term affordability lies at the heart of the coverage problem. A child treated at age three may remain enrolled with a health plan for only a few years before the family changes jobs or coverage, meaning the insurer that pays for the cure may never capture the savings from avoided care. Economists describe this as a mismatch between who pays and who benefits, and it gives payers a rational incentive to delay or deny coverage in the hope that someone else will bear the cost. For families, the consequence is that access can depend on the accident of which insurance plan covers a child in a given year.

The commentary also examines the frontier of ultra-rare disease, where the economics become even more difficult. Landmark cases such as patient-specific in vivo gene editing for a rare genetic condition and patient-customized oligonucleotide therapy, each developed for a single individual, have demonstrated that bespoke treatments are technically feasible. But therapies designed for one or a handful of patients will never recoup their development costs through sales, no matter how high the price. The authors point to proposed funding approaches for N-of-1 trials of individualized gene-targeted therapies and to efforts to overcome barriers to commercially pre-viable gene and cell therapies for rare and ultra-rare diseases as signs that researchers and policymakers are searching for models that do not depend on conventional market returns.

Regulatory innovation is moving in parallel. The FDA has launched a framework for accelerating the development of individualized therapies for ultra-rare diseases, an acknowledgment that the agency’s traditional pathways were designed for drugs manufactured at scale rather than treatments built for one patient. On the payment side, the Centers for Medicare and Medicaid Services have expanded access to gene therapies through innovative state agreements, and proposals for a national benefit for cell and gene therapies have been advanced in health policy forums. These arrangements, including outcome-based contracts in which manufacturers receive full payment only if a therapy works as promised, represent early attempts to spread risk between manufacturers, payers, and the public.

For the pediatric community, the stakes are unusually high because timing matters in a way it does not in adult medicine. Many of the conditions targeted by gene editing are progressive, and the therapies work best, or only, when administered before irreversible organ damage occurs. Newborn screening programs increasingly identify affected infants in the first days of life, creating a narrow window in which regulatory approval, insurance authorization, manufacturing capacity, and clinical delivery must all align. A delay of months in coverage negotiation can convert a curative intervention into a palliative one, which is why the authors frame payment policy as an integral component of the therapy itself rather than an administrative afterthought.

The commentary closes with a call to build the policy environment deliberately rather than reactively. The authors argue that without coordinated action on coverage, reimbursement, and financing, the remarkable science described by Pan and colleagues will reach only a fraction of the children who could benefit, and that uncertain payment prospects may deter investment in therapies for the rarest conditions of all. The tools of molecular biology have, in their telling, largely been proven; the rulebook that determines who can use them is still being written, and the next chapter will be drafted not by geneticists but by policymakers, insurers, and the families advocating for their children.

Subject of Research: Insurance coverage and reimbursement policy for pediatric gene and cell therapies

Article Title: Editing the rulebook: building the policy environment for children to access gene therapy

Article References: Pulcini, C. D., Chua, K.-P., Conti, R. M., On behalf of the Pediatric Policy Council, Keller, D., Montez, K., Ragavan, M., Lorch, S., Plax, K., Cheng, T., Geme, J. S., Lakshmanan, A., & Mariani, T. J. (2026). Editing the rulebook: building the policy environment for children to access gene therapy. Pediatric Research. https://doi.org/10.1038/s41390-026-05588-y

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05588-y

Keywords: gene therapy, CRISPR, pediatrics, health policy, insurance coverage, drug pricing, rare disease, sickle cell disease, spinal muscular atrophy, reimbursement, base editing, ultra-rare disease