In 2025, an infant known as Baby KJ became one of the first patients to receive a personalized CRISPR-based gene-editing therapy, specifically designed to correct the mutation causing his life-threatening Carbamoyl phosphate synthetase (CPS1) deficiency. This rare metabolic disorder prevents the body from properly clearing ammonia which could lead to rapid toxicity and death without intervention. In an unprecedented six-month effort, researchers at the Children’s Hospital of Philadelphia (CHOP), the University of Pennsylvania, and other collaborators engineered a custom base-editing treatment tailored to KJ’s unique genetic error. The FDA reviewed the application on an accelerated timeline and allowed the investigational therapy to proceed in just one week, reflecting a high degree of regulatory flexibility toward individualized medicine.
KJ’s successful treatment showcased not only the technical feasibility of personalized gene editing, but also the potential for dramatically shortening drug development timelines from years into just months. While this case illustrates what is possible under highly coordinated and flexible conditions, it also raises an urgent question: what would it take to make this kind of outcome reproducible? Addressing that challenge will require more adaptive regulatory frameworks, scalable manufacturing strategies, and stronger collaborations amongst sectors. His story signals a new paradigm in how individualized therapies can be regulated and delivered moving forward.
The implications of KJ’s treatment extend far beyond rare disease. In oncology, therapies such as chimeric antigen receptor T-cell (CAR-T) therapy and tumor-infiltrating lymphocytes (TILs) rely on using a patient’s own immune cells to recognize and attack cancer. Similar to KJ’s therapy, these approaches are highly personalized and biologically complex, making it difficult to fit within traditional development and regulatory models. As a result, cell and gene therapies are increasingly being developed with modular design principles in mind. For example, gene editing tools like CRISPR can be adapted to correct different mutations, while CAR-T therapies can be engineered to target different tumor antigens. This highlights the potential for more scalable, platform-based development; however, in practice, most therapies today are still developed and evaluated largely on a product-by-product basis, limiting the efficiency gains these approaches could enable.
Together, these examples illustrate a broader challenge: scientific innovation is advancing faster than the systems designed to support it. Across both cell and gene therapies, the obstacles that remain are less about biological feasibility and more about the structural frameworks surrounding development. These barriers largely stem from two core issues: regulatory frameworks that are not yet optimized for highly individualized therapies, and manufacturing and access barriers that limit their ability to scale.
Among these challenges, the regulatory landscape remains an important factor shaping the broader implementation. Existing regulatory frameworks were largely designed around traditional, large-scale drug development models rather than therapies that are inherently individualized and tailored to a single patient. There is growing recognition within the regulatory community of the need to evolve. Emerging discussions around the FDA’s plausible mechanism framework and efforts to support more flexible, context-dependent evidence generation reflect a shift toward approaches better suited to individualized therapies. Recent FDA discussions have also highlighted the importance of “right-sizing” evidentiary expectations, calibrating what is required to the specific context of a therapy rather than applying a one-size-fits-all standard.
In public comments on the FDA’s draft guidance regarding the plausible mechanism framework, Friends of Cancer Research (Friends) emphasized that while individualized therapies such as gene editing and antisense oligonucleotides hold transformative potential, they also present unique challenges under traditional approval paradigms due to extremely small patient populations and constraints around evidence generation. Friends supported greater regulatory flexibility but also stressed the need for clearer guidance on evidentiary sufficiency, scalable CMC expectations, and the use of real-world and post-market evidence to support the long-term development of individualized therapies.
These regulatory uncertainties contribute to a broader challenge within the field: the gap between early clinical promise and the level of evidence required to achieve full approval. Often referred to as the “valley of death,” this gap continues to create significant obstacles for promising therapies. Friends have been at the forefront of efforts to close this gap, consistently translating multi-stakeholder discussions into concrete regulatory proposals. More recently, Friends collaborated with the Parker Institute for Cancer Immunotherapy (PICI) on a 2025 White Paper proposing specific frameworks for aligning regulatory flexibility with manufacturing adaptability to expand patient access to genetically modified cell therapies. Friends has explored new clinical trial designs, such as evaluating multiple gene modifications simultaneously, to overcome the limitations of traditional drug development models. This could reduce the need for full redevelopment for each manufacturing change, and it could meaningfully compress development timelines and lower barriers to access. These efforts reflect a broader shift toward more flexible, platform-based approaches to development that can better support scaling individualized therapies.
Even where regulatory pathways become more flexible, manufacturing and access barriers remain formidable bottlenecks. Cell therapies require complex, multi-step manufacturing processes. Variability in starting material, vector design, and processing conditions can all affect the final product, making consistency and scalability challenging. These complexities also drive up costs, with fewer than one-quarter of eligible patients currently receiving these therapies due to logistical and financial barriers. The Friends Cell Therapies Webinar for Advocates in 2025 and Public Meeting in 2025 surfaced these issues directly, with financing, reimbursement, and manufacturing infrastructure all playing a role in limiting patient access to these therapies. At the same time, companies are often hesitant to invest in therapies targeting small patient populations without predictable regulatory pathways and clear financial incentives or return on investments. Policy solutions enabling decentralized or point-of-care manufacturing could help bridge this gap, in part, by bringing manufacturing and delivery closer to patients.
Looking ahead, several scientific and regulatory challenges remain. From a biological standpoint, biological risks such as off-target gene editing and unintended long-term effects must be carefully managed. In oncology, development of cell therapies for treatment of solid tumors remains particularly challenging due to factors such as tumor microenvironment suppression, poor T-cell infiltration, and antigen heterogeneity. While these scientific challenges are important for advancing cell and gene therapies, they also reinforce the need for tailored regulatory and manufacturing frameworks that are flexible enough to support continued innovation while maintaining patient safety and product quality.
Ensuring these conditions exist for patients is what drives the work of Friends. By convening stakeholders, generating policy solutions, and advocating for science-based regulatory evolution, Friends is helping to shape a future where breakthroughs like KJ’s are not one-off successes but sustainable realities. Baby KJ’s story shows what is possible when science, collaboration, and urgency align. The challenge now is ensuring that this level of innovation becomes the norm – not the exception.
Sonia Seth is a Junior at George Washington University studying Public Health and was an undergraduate intern at Friends of Cancer Research in 2025-2026.