Science Digest: Scaling Cell & Gene Therapies

Momentum, Barriers, and What Comes Next

Team KC Laboratory Informatics Consultants Amanda Kailher and Felicia Loi break down the tension between scientific promise and breakthroughs in the cell and gene therapy space, and the commercial reality and limitations surrounding high cost and a shifting global landscape.

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State of Cell & Gene Therapy Today →

Over the past four decades, cell & gene therapies have evolved from a bold scientific concept into both a transformational and challenging area in modern biotechnology. The 1980s and 1990s marked the field's foundational era, culminating with the first successful human gene therapy trial in which researchers introduced a functional copy of the ADA gene into the immune cells of patients with SCID (Severe Combined Immunodeficiency), demonstrating that targeted genetic correction was possible.

Early milestones set the stage for rapid advances in vector engineering, genomic technologies, and ex vivo manipulation, which accelerated through the 2000s and catalyzed the personalized medicine wave we recognize today. By the early 2010s, breakthroughs in delivering CAR-T cell therapy for cancer treatment transformed theoretical promise into clinical reality. They paved the way for FDA approvals that enabled the modern era of cell and gene therapy. 

Today, the enthusiasm that defined the late 2010s has largely given way to a correction in industry expectations. Investor sentiments have drifted, with a wave of cell & gene therapy companies either shutting down or consolidating, as documented in the 2025 Biotech Graveyard analysis by Fierce Biotech. What pressures contribute to fluctuating industry confidence? The science is solid, the commercial path is not. Manufacturing costs remain high, reimbursements and cost barriers slow adoption, and delivery effectiveness varies widely across therapies. 

As the industry recalibrates, staying ahead of the trends is not an option; it's essential for Team KC. Many of our clients operate in the cell & gene therapy space, and the complexity of their work requires us to understand not just the science but also the evolving landscape around us.

Our perspective shapes how we evaluate tools, workflows, and data strategies, and we’ve identified several challenges that are emerging as defining tension points for the next phase in the cell & gene therapy space.

The High Cost & Reimbursement Puzzle →

The cost of cell and gene therapies remains a significant barrier to adoption, particularly in rare diseases, where patient populations are small and development costs are high. Many therapies require upfront payments of $ 1 to $2 million, which directly conflict with a system designed for chronic therapies administered over months and years. Coverage is further constrained by restrictions of payer criteria, creating delays and disparities in patient access. 

Restrictive coverage policies and fragmented payment methods exacerbate access barriers by using narrow clinical trial criteria, labeling accelerated-approval therapies as “experimental,” and distinguishing between inpatient and outpatient treatment, according to a recent spotlight on coverage challenges. 

The above article focuses on reframing how the value of cell and gene therapy is assessed. Arguing that the reduced caregiver burden and improved quality of life would have overall societal and economic benefits, which traditional health technology assessments undervalue. 

While there are ongoing discussions pushing to reframe these assessments, payment reform alone is not sufficient to unlock access.

Even when coverage pathways exist, the ability to deliver cell and gene therapies at scale is limited by fundamental manufacturing and operation constraints.

Manufacturing and Scalability Bottlenecks →

While reimbursement and coverage policies determine whether cell and gene therapies are paid for, scalability ultimately determines whether therapies can be delivered to patients at a meaningful scale. Highly individualized therapies necessitate highly individualized manufacturing processes.

Unlike traditional biologics, these multi-step, complex manufacturing processes have limited production capacity and rely on specialized facilities and highly trained labor. As a result, production capacity cannot be increased rapidly in response to demand. This limitation is increasingly cited in recent literature as a primary barrier beyond initial regulatory approval.

These constraints are particularly pronounced for gene therapies dependent on viral vectors for safe delivery. Manufacturing challenges include long lead times, batch-to-batch variability, and limited biological understanding of how cells produce vectors and how stable they remain during manufacturing to scale. Current AAV (adeno-associated virus) manufacturing methods were developed for early-stage production, not industrial-scale manufacturing. 

Without predictable, mappable processes and robust process control, attempts to scale introduce variability that large manufacturers would struggle to manage. 

Integration Into Clinical Practice →

The transition of cell and gene therapies from specialized academic centers into broader clinical settings remains a pivotal bottleneck. While several therapies have received regulatory approval, their real-world integration into community-based clinics lags. This exposes a persistent gap between innovation and implementation.

Several factors contribute to this expansion. One persistent barrier is perception. Many patients (and their referring clinicians) still view these therapies as "too experimental" or "too risky". Even with approvals in place, integrating these systems into broader clinical practice requires specialized components, including cell manufacturing coordination, stringent supply chain logistics, toxicity management, and long-term follow-up care. These capabilities are more common in academic institutions than in community practice.

That said, emerging models and examples illustrate how innovation can drive accessibility. In a recent review of progress in skin gene therapy, researchers highlighted how recessive dystrophic epidermolysis bullosa (RDEB), first described in 1879 and long treated only palliatively, has become a test case for how new cell and gene technologies can transform inherited diseases once considered untreatable. The authors noted, "as new technologies emerged, [treatment] offered efficacy but required specialized medical professionals and infrastructure… [while] HSV-1 helps alleviate the problem of resource and infrastructure-intensive treatments…the problems of cost, scale, and delivery over large surface areas will drive progress and promote new solutions."

Scientific Frontiers and Technical Barriers →

Cell and gene therapies are game changers, but the journey is full of hurdles. Take Car-T therapy, for example. It can wipe out blood cancers, but tumors are sneaky. In a study on antigen escape, researchers discuss new approaches to transform CAR-T cells into immune catalysts rather than single-target killers, activating the patient's own immune system to attack multiple tumor antigens and reduce the risk of relapse.

Delivery is another key bottleneck. While blood cancers are relatively accessible, reaching organs like the brain or certain solid tumors remains difficult. Yet a recent study shows promise on this front. In a mouse model of rare leukodystrophy, a gene therapy delivered systemically crossed the blood-brain barrier, reversing brain swelling and restoring motor function. 

Safety also remains a central concern. "On-target, off-tumor" effects can harm healthy tissues, so new designs are being built with tissue-specific activation and safety switches to keep therapies precise. In a study on glioblastoma, scientists combine CAR-NK cell therapy with checkpoint inhibition to reshape the tumor microenvironment – triggering a stronger immune response where single therapies had failed.

The bottom line? The science of cell and gene therapies is thrilling, but many hurdles remain. Cracking antigen escape, perfecting delivery, and keeping safety top of mind are all essential if these therapies are going to reach more patients beyond academic hospitals. Despite these challenges, the field is moving fast. The next wave of breakthroughs could transform patient care and redefine what is possible in medicine.

A Shifting Global Landscape →

For years, the United States has set the pace for genetically modified cell therapies. It was the birthplace of CAR-T, backed by a robust biotech infrastructure and a regulatory environment that supports early and bold innovation.

While this leadership was long undisputed, the landscape is changing. Other geographies, such as China, are rapidly advancing and reshaping the global playing field.

Recent ASGCT and Citeline data highlight just how quickly the landscape is expanding beyond the United States. More than 4,000 cell, gene, and RNA therapy programs are now in clinical or preclinical development worldwide. Regulatory approvals are rising across multiple regions. As of the end of March, 33 gene therapies are approved worldwide, including 23 within the United States and 10 in countries such as China, the Philippines, Japan, and Russia. This is further proof that growth is no longer concentrated in the United States. Countries in Asia and the EU are building substantial pipelines, broadening into new disease areas, and accelerating activity in RNA and allogeneic cell therapies.

As a result, commercial realities are shifting. China's high trial volumes and large domestic patient base are reducing development and manufacturing costs, which could introduce new pricing and reimbursement pressures in the United States. At the same time, global players are tapping into these emerging markets to reach larger populations, speed up enrollment, and localize manufacturing. Biotech and pharma companies must begin to view other major markets not only as license-in territories but as emerging competitors. As countries like China scale up their manufacturing and R&D, everything from global logistics to localization strategies to partnership structures may need to evolve.

That said, these emerging markets still face hurdles, including regulatory variability, quality-control concerns, and geopolitical complexities. Even with these factors, countries like China are scaling up R&D and manufacturing at a pace that is reshaping expectations across the global value chain. Everything from international logistics and localization strategies to partnership structures may need to evolve to keep pace.

The key takeaway: the global commercial landscape for cell and gene therapy is evolving from being U.S.-dominated to a multipolar ecosystem. For stakeholders, competition, regulation, cost dynamics, and partnership models are all shifting. Success in cell and gene therapies will depend not only on scientific strength but also on a globally oriented strategy. This shift could accelerate innovation across the field.

Where does Team KC come in? →

Cell and gene therapies don’t struggle because the scientific opportunity is falling short; they struggle when the systems around them can’t keep up. From reimbursement pitfalls to manufacturing bottlenecks, the challenges are deeply interconnected.

The paths our clients are on don't end at early development, which is why Team KC stays on top of where the field is headed, not just where it is today. As consultants who are scientists first, we stay deeply engaged with the technical realities of the industry to “speak the same language” and help design foundations that grow from concept to clinic, and beyond. Future-proofing isn’t about predicting every outcome, but preparing for what might come next. 

Interested to learn more about how we serve our clients in the Cell & Gene Therapy space? We’d love to connect - fill our contact form to start the conversation.