Gene Therapy Advances: New Delivery Platforms, Manufacturing Growth and Preclinical Data

Researchers reported progress in gene therapy delivery with a novel DES-AAV-Foxo1 system for corneal endothelial dysfunction and MSC-based delivery of retroviral replicating vectors for peritoneal mesothelioma, while the field shifts toward nonviral platforms such as lipid nanoparticles. Utilization rates for gene therapies have grown 42%, and per-member-per-year (PMPY) spend doubled from 2022 to 2024, according to trends in a health data set covering 300 million people in the U.S. The cell and gene therapy contract manufacturing market is projected to expand from $4.31 billion in 2026 to $9.08 billion by 2031.

Every gene therapy and most cell therapies depend on a viral vector, typically AAV or lentivirus, to deliver genetic material into a patient's cells, and vector production is the single tightest capacity constraint in the industry. Lonza has expanded its dedicated viral vector facilities in Houston and Visp, Switzerland by roughly 50 percent in 2024 and 2025 to meet demand. In 2024, Novo Holdings paid $16.5 billion for Catalent, the largest deal in CDMO history, while Thermo Fisher committed a separate $2 billion, four-year capital program to its own vector manufacturing infrastructure. Together with Samsung Biologics and Charles River Laboratories, these five companies now account for the large majority of global vector production revenue.

The field is experiencing a paradigm shift as it moves away from viral vectors, which are the most mature technology from a clinical perspective, and towards nonviral systems such as lipid nanoparticles (LNPs) and extracellular vesicles (EVs), owing to their widely tailorable biochemical properties and superior safety profiles. AAV vectors remain the clinical benchmark for in vivo gene delivery, owing to their high transduction efficiency and durable expression. However, their limitations — including limited cargo capacity, immunogenicity and genotoxic risk — define the boundaries that next-generation systems must overcome. Data from clinical trials show that gene therapies using viral vectors for delivery can cause genotoxicity, specifically insertional mutagenesis that can activate oncogenes, in a subset of patients. While no LNP-based gene therapies are presently FDA-approved, many are in clinical trials.

The therapy-developer layer remains oncology-heavy today, but gene therapy for rare disease is the fastest-growing segment behind it, driven by a rising pace of regulatory approvals for conditions that previously had no treatment option at all. Currently, there are more than 40 gene therapy products on the market, treating conditions like hemophilia, cancer, and various rare diseases. According to the 2025 Cell and Gene Therapy Report: Advancing the Future of Medicine, 178 oncology-focused drug candidates entered the late-stage pipeline in the past year alone. Medicare reimburses roughly $269,000 for inpatient CAR-T administration, while the drug itself frequently costs more than $400,000, a gap partially closed by New Technology Add-on Payments. The CAR-T therapy Carvykti, developed and marketed with Johnson & Johnson, treated more than 10,000 patients for multiple myeloma and is targeting company-wide profitability in 2026.

Researchers engineered an AAV-Foxo1 delivery system using a viscous choline chloride-fructose-based deep eutectic solvent (DES) as the carrier for corneal endothelial dysfunction, a condition with an estimated 12.7 million patients awaiting corneal transplantation. The DES-AAV-Foxo1 delivery system exhibited good biocompatibility, significantly prolonged anterior chamber retention, and enhanced transfection efficiency in corneal endothelial cells compared to conventional AAV delivery. Animal experiments confirmed that it effectively improved corneal endothelial pump activity and mitigates endothelial dysfunction in type 1 diabetes mellitus and Fuchs endothelial corneal dystrophy mouse models.

In a feline model of alpha-mannosidosis, systemic AAV gene therapy was evaluated in animals with advanced disease. Some improvements in clinical parameters were observed, however these improvements were less than in animals with less advanced disease. Although the treated animals were improved compared to untreated animals, increasing the vector dose did not further improve clinical outcomes. Partial correction extended the lifespan of diseased cats and may be medically beneficial to patients by slowing or stabilizing the progressive degenerative course of disease.

Separate research on recombinant adeno-associated virus (rAAV) vectors used in human trials as carriers of vaccines for HIV-1 showed that in mice, rAAV vectors expressing the gene encoding HIV-1 gag stimulated gag-specific CD8+ T cells, but these T cells failed to expand after a booster immunization with a replication-defective adenoviral vector also expressing gag. The rAAV vector-induced CD8+ T cells proliferated poorly, produced low levels of IFN-γ in response to gag stimulation, and upregulated immunoinhibitory molecules. The impaired proliferative capacity was caused by persistence of the antigen-encoding rAAV vectors and could be reversed by placing the CD8+ T cells in an antigen-free environment. The data suggest that rAAV vectors induce functionally impaired T cells and could dampen the immune response to a natural infection.

For cancer gene therapy, researchers investigated the use of tumor-homing mesenchymal stem cells (MSCs) as RRV carriers in a clinically relevant model of malignant peritoneal mesothelioma. MSCs derived from adipose tissue, bone marrow, and umbilical cord demonstrated significant migration toward mesothelioma cells and were permissive to RRV infection and production. In peritoneally disseminated cancer models, MSC/RRV delivery significantly enhanced intratumoral viral transmission, and in ascites-mimicking models it achieved superior antitumor efficacy, resulting in robust tumor suppression and prolonged survival. RRV-mediated suicide gene therapy has demonstrated efficacy against a variety of cancers, including glioma, mesothelioma, lung cancer, gastric cancer, pancreatic cancer, ovarian cancer, and osteosarcoma.