Gene therapy has transformed from a bold scientific idea a mere few decades ago into a leading therapeutic modality with the potential to treat and even cure diseases once thought untreatable. Within this broader evolution, adeno-associated virus (AAV) vectors have emerged as one of the most successful delivery mechanisms, shaping modern gene therapy development and manufacturing. Today, companies like Forge Biologics play a critical role in turning AAV-based therapies into real-world medicines, bridging innovation with large-scale, compliant production.
The Origins of Gene Therapy
The concept of gene therapy, which is correcting or modifying genetic material to treat disease, can be traced back to fundamental discoveries in molecular biology in the mid-20th century. The identification of DNA as the molecule of heredity opened the door to the idea that introducing functional genes into cells could correct genetic disorders. Early efforts focused on understanding gene transfer systems and viral vectors capable of delivering genetic material into host cells.
Throughout the 1970s and 1980s, researchers explored a variety of viral systems for gene therapy delivery, but it wasn’t until the late 1980s that AAV drew significant interest. Initially discovered in the 1960s as a contaminant in adenovirus preparations, AAV was recognized for its non-pathogenic nature and ability to infect both dividing and non-dividing cells. These key features would later make AAV a preferred gene therapy vector.
The potential of AAVs has been shown through their use in well over 225 clinical trials and the FDA’s approval of six AAV-based gene therapy products to date, positioning these vectors at the forefront of the field.
AAV: From Discovery to Therapeutic Platform
AAV’s journey from the lab to therapies for patients reflects decades of scientific progress. In the early 1980s, molecular biologists successfully cloned AAV genomes into plasmids, enabling controlled manipulation of the virus for gene delivery research. These developments laid the groundwork for using recombinant AAV (rAAV) vectors, which replace viral genes with therapeutic payloads while retaining key genetic elements required for packaging and delivery.
By the 1990s, proof-of-concept studies demonstrated that rAAV could deliver genes in animal models, including sustained expression in vivo. Early clinical work, such as rAAV-mediated delivery for cystic fibrosis and neurological disease models, showed promising proof of principle.
As the field evolved, AAV vectors were increasingly applied to clinical targets with well-defined genetic causes. Over the last decade, AAV-based therapies have reached major regulatory milestones with several commercial approvals, including ZOLGENSMA® for spinal muscular atrophy, among other gene therapies now approved in the U.S. and abroad.
Why AAV Became the Go-to Vector
AAV’s success in gene therapy stems from key biological characteristics highly conducive to clinical use, such as:
These and other features allowed AAV to become a dominant platform in animal studies in a growing number of clinical programs addressing rare and prevalent inherited disorders.
FDA Approved AAV Gene Therapies
To date, the FDA has approved a growing number of AAV gene therapies, representing important milestones in the treatment of patients with serious diseases, including inherited retinal disorders, neuromuscular diseases, hemophilia, and rare neurologic conditions. These therapies leverage AAV vectors to enable durable gene expression following a single administration, offering the potential for long-term clinical benefit.
These are the therapies approved as of January 2026, searchable in the Purple Book, the official FDA database of licensed biological products, including gene therapies.
The advancement of AAV gene therapies from early development to FDA approval reflects significant progress in vector engineering, manufacturing scalability, clinical execution, and regulatory alignment. Collectively, these approved products establish a foundation for the continued expansion of AAV gene therapy into late-phase development and commercial use.
The Manufacturing Process for AAV Gene Therapies is Complex
While the promise of gene therapy has accelerated clinical development, translating these therapies into scalable, reliable products increasingly depends on AAV manufacturing success. Unlike traditional small molecules (used for medicines like aspirin and antibiotics), viral vectors are biologically complex and require living systems for production, presenting unique manufacturing challenges.
AAV manufacturing is a multi-stage process and includes, among other steps:
Because AAV vectors are complex biological entities, manufacturing must be highly controlled and consistent, especially as therapies transition from small clinical trials to broader commercial supply.
Scaling Manufacturing for a Growing Pipeline
As AAV therapies expand beyond rare diseases into broader indications, the demand for scalable, cost-effective manufacturing has grown dramatically. Today, more than 65% of gene therapies in development use AAV vectors, underscoring the need for manufacturing platforms capable of delivering high yields at commercial scale.
The industry has progressed from early laboratory techniques to suspension cell culture systems, scalable bioreactors, and advanced purification technologies that support larger batch sizes and improved reproducibility. These innovations help reduce bottlenecks that historically constrained gene therapy production.
Despite progress, some challenges remain: analytical tools, process characterization for late-phase, and scale-up strategies continue to evolve to meet regulatory expectations and market needs.
Industry Impact and the Role of CDMOs
Contract Development and Manufacturing Organizations (CDMOs) have become vital players in enabling gene therapy developers to navigate this complex landscape. CDMOs specialize in scalable production platforms, regulatory compliance, and process optimization, allowing innovators to focus on therapeutic discovery and clinical development.
AAV manufacturing at scale requires deep technical expertise, from plasmid design and cell line optimization to purification and fill-finish operations. The evolution of manufacturing technology has enabled a transition from small, experimental batches to commercial-grade production capable of supporting global clinical and market demand.
Forge Biologics in Today’s AAV Manufacturing Ecosystem
Within this global ecosystem, Forge has emerged as a leading AAV CDMO, strategically positioned to support the next generation of gene therapies. With a facility in Ohio dedicated to AAV and designed for scalable production, Forge combines advanced manufacturing platforms with deep gene therapy expertise to help clients move from concept to clinic, and beyond.
Forge leverages proprietary technologies that enhance yield and process performance. This includes optimized vector production systems and robust analytical capabilities that ensure consistency and quality across serotypes and scales, a critical foundation for commercial production and regulatory success.
Forge’s integrated approach reflects the broader trajectory of the gene therapy field: shifting from early proof-of-concept to commercial manufacturing. By advancing manufacturing capabilities alongside therapeutic innovation, Forge contributes to bringing transformative medicines to patients worldwide.
The Future of Gene Therapy Manufacturing
Over the past several decades, gene therapy has progressed from a theoretical concept to a proven therapeutic modality, with AAV vectors at the forefront of clinical success. Advances in manufacturing have mirrored scientific progress, evolving from small research systems to highly regulated, scalable platforms that can support global demand.
As the number and diversity of AAV-based therapies continue to grow, so too does the need for manufacturing solutions that deliver quality, scalability, and reliability. In this landscape, companies like Forge play an essential role, enabling innovators to realize the promise of gene therapy, from early development through commercial supply.
The history of gene therapy is also a story of manufacturing evolution. As we look to the future, AAV manufacturing will remain a cornerstone of the industry’s ability to deliver safe, effective, and accessible treatments to patients around the world.