Gene and Cell Therapies Enter a New Era: From Revolutionary Treatments to Market Realities

The Great Cell and Gene Therapy Reckoning: From Revolutionary Promise to Industry Crossroads

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As personalized CRISPR therapies arrive and CAR-T cells target solid tumors, the field confronts manufacturing challenges and soaring costs

The gene and cell therapy revolution that scientists have promised for decades is finally materializing—but not quite in the way many had envisioned. In 2025, the field stands at a pivotal crossroads, celebrating historic medical breakthroughs while grappling with formidable economic and manufacturing obstacles that threaten to limit patient access to these potentially life-saving treatments.

A Landmark Year for Personalized Medicine

In February 2025, an infant known as KJ became the world's first patient to receive a fully personalized CRISPR gene editing therapy at Children's Hospital of Philadelphia. Born with severe carbamoyl phosphate synthetase 1 (CPS1) deficiency, a rare metabolic disease, KJ received a customized base editing therapy delivered via lipid nanoparticles. Within six months, researchers designed and manufactured the bespoke treatment, and within seven weeks after infusion, KJ could tolerate increased dietary protein and required half the starting dose of his medication.

This achievement represents more than a single patient's recovery—it demonstrates that gene editing technology can be rapidly adapted for individuals with ultra-rare diseases affecting perhaps only dozens of people worldwide. The case provides a pathway for gene editing technology to be successfully adapted to treat individuals with rare diseases for whom no medical treatments are available.

Meanwhile, CRISPR-based therapies continue to expand their reach. Casgevy, the first approved CRISPR medicine for sickle cell disease and beta-thalassemia, has now received approval in the U.S., UK, EU, Switzerland, Canada, Bahrain, Saudi Arabia, and the United Arab Emirates. Clinical data from 17 patients with sickle cell disease and 27 patients with beta-thalassemia show dramatic and durable results.

In another groundbreaking development, Prime Medicine announced positive results in May 2025 from treating a patient with chronic granulomatous disease using prime editing—the first clinical data showing the efficacy and safety of this advanced CRISPR technique in humans.

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SIDEBAR: Breaking the "Immune Desert" in Prostate Cancer

For decades, prostate cancer has resisted immunotherapy attempts, earning the nickname "immune desert" because of its tumor microenvironment's ability to exclude therapeutic T cells. But recent advances in CAR-T cell therapy are beginning to crack this formidable challenge.

In 2024, researchers published results from a first-in-human phase 1 trial of prostate stem cell antigen (PSCA)-directed CAR-T cells in men with metastatic castration-resistant prostate cancer (mCRPC)—a disease that kills more than 34,000 American men annually and no longer responds to hormone therapy.

The results, though preliminary, offer hope. Four out of 14 patients experienced PSA declines of 30% or more, with one patient achieving a greater than 90% decline during the 28-day monitoring period, along with shrinking tumors in bones and soft tissue. Five patients experienced mild or moderate cytokine release syndrome, a treatable side effect.

Targeting the Right Antigens

Key therapeutic approaches include CAR-T cell therapy targeting tumor antigens such as prostate-specific membrane antigen (PSMA) and prostate stem cell antigen (PSCA). PSCA is particularly attractive because it is highly expressed in prostate cancer and increases with advanced disease states, especially in bone metastases.

Researchers at Fred Hutchinson Cancer Center have developed an alternative approach. They engineered CAR-T cells targeting STEAP1, a molecule expressed more uniformly across tumor cells from advanced prostate cancer than PSMA. When combined with a drug that focuses an immune-boosting molecule within tumors, the CAR-T cells more effectively reduced prostate tumor growth and helped prevent tumors from escaping immune attack.

Overcoming Persistence Problems

A significant challenge emerged in the City of Hope trial: CAR-T cells did not persist at high levels beyond the 28-day monitoring period, which limits the therapy's effectiveness—a common challenge in solid tumor CAR-T therapy. Researchers are addressing this in follow-up trials, exploring combinations with radiation therapy to enhance anti-tumor activity.

Advances in nanoparticle-based gene delivery systems and combination therapies involving gene and cell therapies with immunotherapies hold potential for synergistic treatment effects. Studies have shown that combining CAR-T cells with immune checkpoint inhibitors like anti-PD-1 or anti-CTLA-4 antibodies can restore T cell activity and promote tumor regression.

A More Intensive Treatment

Despite the promise, experts caution that CAR-T therapy for prostate cancer represents a different treatment paradigm. Medical oncologist Dr. David Einstein notes that lymphodepletion can leave patients vulnerable to infections, and given the added risk of cytokine release syndrome, CAR-T will likely be suitable "only for a selected group of patients".

Still, for men with advanced prostate cancer who have exhausted other options, these emerging therapies offer something previously unavailable: hope for a new treatment avenue in a disease that has long resisted immunotherapy's transformative power.

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The Push Beyond Blood Cancers

While CAR-T cell therapies have revolutionized treatment for blood cancers, their application to solid tumors has remained elusive—until recently. After a decade of relatively modest results for solid tumors, recent clinical trials have started to yield promising outcomes in glioblastoma and other challenging solid tumor entities.

In Q1 2025, Iovance's Amtagvi became the first approved cell therapy for solid tumors, specifically for melanoma, and Adaptimmune's Tecelra gained FDA approval as the first engineered T cell receptor therapy. These approvals signal a potential turning point for the field.

However, formidable challenges remain. CAR-T cell therapy effectiveness in solid tumors has been limited by factors including antigenic heterogeneity and the immunosuppressive nature of the tumor microenvironment. Researchers are exploring innovative strategies, including enhancing T cell persistence and cytotoxicity, targeting multiple antigens, and combining CAR-T therapies with immune checkpoint inhibitors.

Regulatory Momentum and Market Expansion

The regulatory landscape is accelerating. In 2024, the FDA approved eight novel cell and gene therapies and at least six new indications for existing therapies, an increase from prior years and an encouraging signal that the FDA is on track to meet its projection of approving 10 to 20 such therapies annually by 2025.

Notable 2025 approvals include Abeona's Zevaskyn, the first cell-based gene therapy for recessive dystrophic epidermolysis bullosa, a devastating skin disorder, and Precigen's Papzimeos, the first therapy approved for recurrent respiratory papillomatosis.

Globally, there are now 36 approved gene therapies, 71 non-genetically modified cell therapies, and 36 RNA therapies. The clinical pipeline is robust: the global landscape includes 1,905 ongoing clinical trials in the first half of 2025, with significant activity across North America (844 trials), Europe (453), and Asia-Pacific (750).

Perhaps most significantly, the FDA is embracing accelerated approval pathways for gene therapies. Peter Marks, the former director of the FDA's Center for Biologics Evaluation and Research, vocally supported increased use of the Accelerated Approval program, stating there would be "increasing receptivity" and that CBER was "leaning in".

Diversification Beyond Oncology

The field is experiencing a notable shift in focus. While only one new therapy (Tecelra for synovial sarcoma) was approved in Q3 2024, deeper in the pipeline, 51% of newly initiated gene therapy trials are now for non-oncology indications, up from just 39% year-over-year.

This diversification includes promising applications in autoimmune diseases, cardiovascular conditions, and neurological disorders. CRISPR Therapeutics is expanding trials for CTX112 in systemic lupus erythematosus to include patients with systemic sclerosis and inflammatory myositis, while companies are developing therapies for familial hypercholesterolemia and other cardiovascular conditions.

The Manufacturing Crisis

Despite these advances, the field faces a critical challenge that threatens to limit patient access: manufacturing. Peter Marks stated that gene therapies are at a "critical juncture" due to manufacturing challenges, noting that "the setup cost for these small gene therapies is just way too high in proportion to the return on investment".

The numbers are sobering. Analysis by the Institute for Clinical and Economic Review suggests the average cost of a gene therapy is between $1 million and $2 million per dose, with cell therapy costs averaging $1 million per treatment. For therapies like Hemgenix for hemophilia B, which costs $3.5 million per dose, calculations suggest that 500-liter batches produce enough units to treat only 2-3 adult patients, with vector manufacturing costs alone potentially reaching $1-2 million per dose.

The manufacturing complexity stems from fundamental differences with traditional pharmaceuticals. While DNA and viral vectors can be produced at large scales, producing complete products like CAR-T cells currently requires technicians to perform many steps manually. Gene therapies take an average of 15 years minimum for research and development, compared to conventional drugs, and can cost $5 billion to develop—more than five times the average cost of developing traditional drugs.

Financial Headwinds

The economic challenges extend beyond manufacturing. Investment in the sector reached $5 billion in the first half of 2025, though start-up funding has slowed. Financial pressures have led to significant layoffs in numerous CRISPR-focused companies, with firms largely switching focus to getting a smaller set of new products to market as quickly as possible.

The funding environment has been challenging, with investors becoming more selective and cautious. However, certain technologies continue to attract investment. Barcelona-based Splice Bio secured €118 million in series B financing for its next-generation AAV technology, and Danish start-up Fuse Vectors received $5.2 million in pre-seed funding.

Looking Ahead

Despite these challenges, experts remain optimistic. AAV vectors, now proven tools for addressing rare genetic disorders, are increasingly targeting more complex diseases like cardiovascular conditions, with emerging technologies such as AI-enabled vector design and CNS-targeting capsids holding potential.

The field is also benefiting from technological innovations. Northwestern University researchers recently developed a new nanostructure that tripled CRISPR's gene-editing success rates and dramatically reduced toxicity compared to current methods by wrapping CRISPR tools in spherical DNA-coated nanoparticles.

For the gene and cell therapy field to fulfill its promise, stakeholders agree that manufacturing efficiency must improve, regulatory frameworks must evolve, and innovative payment models must emerge to ensure patient access. With industry experts anticipating 30-50 additional cell and gene therapy approvals by 2030, the next five years will determine whether these revolutionary treatments become accessible medicine or remain prohibitively expensive interventions available only to a fortunate few.

The revolution is here—but making it affordable and scalable remains the field's greatest challenge.

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