Infant with Rare Disease Receives Groundbreaking CRISPR Gene Therapy

In a groundbreaking moment for medicine and genetic research, a baby boy named KJ has become the first individual to receive a custom CRISPR gene-editing therapy. This innovative treatment offers a glimpse into the promising future of personalized medicine, particularly for those facing life-threatening genetic conditions.

At the forefront of this historic achievement are researchers Rebecca Ahrens-Nicklas from the Children’s Hospital of Philadelphia and Kiran Musunuru from the University of Pennsylvania. Their work marks a significant milestone; it’s the inaugural instance where a gene-editing treatment was specifically tailored to address a unique, disease-causing mutation present solely in one patient. Ahrens-Nicklas excitedly explained, “He’s showing some early signs of benefit,” although she cautions that it’s still premature to fully assess the treatment’s efficacy.

The rapid publication of the research was motivated by the hope of inspiring other scientists to pursue similar paths. Musunuru emphasized this vision, stating, “We very much hope that showing that it’s possible to make a personalized gene-editing therapy for a single patient in several months will inspire others to do the same.” He believes this landmark achievement may shape the future of treatments for rare genetic disorders, an area currently underrepresented in therapeutic development.

KJ’s condition stems from mutations in both copies of the CPS1 gene, which codes for a crucial liver enzyme. Without this enzyme, ammonia accumulates in the bloodstream when proteins are broken down, posing a severe risk to brain health. The severity of KJ’s condition is underscored by the grim statistic that over half of children born with CPS1 deficiency do not survive infancy. Recognizing the urgency of KJ’s needs, Ahrens-Nicklas and Musunuru developed an innovative base-editing therapy—a form of CRISPR—targeting the liver to reverse one of the genetic anomalies affecting KJ.

In an extraordinary response from regulatory bodies, the researchers contacted US regulators early in the process, seeking a swift path for KJ’s treatment. “They recognized that this was an unusual circumstance,” said Musunuru. The FDA expedited their approval, granting it in just one week after their formal application was submitted when KJ was six months old.

KJ received his first low dose of the treatment in February 2025, followed by increasing doses in the subsequent months. Remarkably, he has been able to tolerate more protein in his diet than ever before, and he requires a reduced dosage of other medications that manage his condition.

Though promising, researchers recognize that ideally, children suffering from conditions like CPS1 deficiency should be treated even earlier to minimize potential long-term damage. Musunuru has a forward-thinking vision, aspiring to develop gene-editing therapies that could be applied even before birth.

In contrast to KJ’s highly personalized treatment, other gene-editing therapies currently available target broad populations, regardless of specific genetic mutations. For example, one of the first approved gene-editing treatments for sickle cell disease operates by enhancing the production of fetal hemoglobin as opposed to correcting the underlying mutations in adult hemoglobin. While effective, this “one-size-fits-all” approach still incurs a significant cost, with treatment courses reaching over £1.6 million in England.

Personalized treatments like KJ’s raise questions regarding future affordability. Although Musunuru refrains from pinpointing an exact cost for KJ’s treatment—thanks in part to contributions from various companies—the expectation is that as technology advances, the associated costs will decrease markedly. “As we get better at doing this, economies of scale will kick in, and you can expect the cost to come down orders of magnitude,” he noted.

Historically, a barrier to developing personalized gene-editing treatments has been regulatory challenges. Different mutations in the same gene have often been treated as separate entities, requiring new approval processes for each unique mutation. Fortunately, there is a growing push towards a “platform approach,” whereby regulatory authorities can grant wide-ranging approvals for therapies aimed at specific conditions, irrespective of the mutation type.

Nick Meade from Genetic Alliance UK underscores the significance of this emerging strategy. “Platform-based approaches, like genome editing with CRISPR – as we’re seeing with KJ’s treatment – offer a scalable way to treat even the rarest diseases. This at last makes treatment a realistic prospect for thousands of families.”