Gene therapy aims to treat or cure diseases at their genetic root by delivering functional genes to replace defective ones, silencing harmful genes, or editing mutations to restore normal function. After decades of setbacks including the tragic death of Jesse Gelsinger in 1999, the field has matured into a clinically validated therapeutic modality. Luxturna (Spark Therapeutics), approved in 2017 for inherited retinal dystrophy, and Zolgensma (Novartis Gene Therapies), approved in 2019 for spinal muscular atrophy, demonstrated that gene therapy could deliver transformative clinical benefits for devastating genetic diseases.
The gene therapy landscape has expanded dramatically with the emergence of CRISPR-based approaches. Traditional gene therapy uses viral vectors to deliver a functional copy of a gene (gene addition), while CRISPR enables direct correction of mutations in situ (gene editing). Intellia Therapeutics demonstrated in vivo CRISPR gene editing in humans with its program for transthyretin amyloidosis, achieving durable protein reduction after a single intravenous infusion. Beam Therapeutics, Verve Therapeutics, and Prime Medicine are advancing base editing and prime editing-based gene therapies that offer precision beyond what standard CRISPR cutting can achieve.
Manufacturing and delivery remain key challenges for the gene therapy field. AAV vector production is complex and expensive, limiting supply and contributing to prices that can exceed $2 million per treatment. Companies like Forge Biologics and Regenxbio are investing in scalable AAV manufacturing platforms. Lipid nanoparticle delivery, which avoids the immunogenicity and packaging size limitations of viral vectors, is emerging as a complementary approach. The combination of improved delivery technologies, more precise editing tools, and scalable manufacturing is steadily expanding the number of genetic diseases amenable to gene therapy intervention.