Gosset Adeno-associated virus serotype 9 Overview
Adeno-associated virus serotype 9 (AAV9) is a non-enveloped, single-stranded DNA virus widely used as a gene therapy vector. It is particularly notable for its high transduction efficiency in cardiac, skeletal muscle, and central nervous system tissues and its unique ability to cross the blood-brain barrier. Recombinant AAV9 vectors are engineered to carry therapeutic gene cassettes flanked by inverted terminal repeats, allowing for stable expression in target cells. AAV9-based vectors have been foundational in the treatment of genetic diseases such as spinal muscular atrophy (with therapies like onasemnogene abeparvovec), Pompe disease, and certain forms of hemophilia. Major safety concerns relate to host immune responses, risk of overexpression toxicities, and challenges associated with large-scale vector production.
Mechanism of Action
Delivers and expresses therapeutic genes by infecting target cells; utilizes capsid tropism for efficient gene delivery, including crossing the blood-brain barrier.
Biological Functions
Disease Associations
Safety Considerations
- Potential for immune responses or pre-existing neutralizing antibodies impacting efficacy
- Dose-dependent toxicity in central nervous system, such as neuroinflammation or neurodegeneration with excess gene expression
- Production scalability and purity for clinical use
- Off-target organ transduction and long-term persistence of vector genomes