AAV1AAV9

AAV1 and AAV9 are serotypes of adeno-associated virus, small non-enveloped DNA viruses used as vectors for gene delivery. They are considered nonpathogenic in humans and have a generally favorable safety profile in research and clinical contexts. Both can package approximately 4.7 kilobases of genetic payload and require helper functions for production.

AAV1 exhibits high transduction efficiency in skeletal muscle and cardiac muscle, making it a focus for muscle-directed gene therapies. AAV9 shows broader tissue tropism, efficiently transducing liver, heart, skeletal muscle, and, under certain conditions, the central nervous system. These differing tropisms influence vector choice for specific therapeutic goals and routes of administration.

Delivery considerations vary by serotype. AAV9 can cross the blood-brain barrier in some models, enabling systemic delivery that reaches the CNS, whereas AAV1 is commonly delivered intra-muscularly or to targeted tissues to maximize muscle transduction. For both serotypes, transgene expression depends on capsid properties, route of administration, and promoter selection, which together shape tissue specificity and duration of expression.

Clinical and research use: Both serotypes are widely employed in preclinical studies and early-phase clinical trials. A notable approved therapy using AAV9 is Zolgensma, which delivers the SMN1 gene for spinal muscular atrophy, illustrating the potential of systemic AAV9 vectors for motor neuron and CNS targeting. AAV1 has been explored in muscular dystrophy and other muscle diseases, often in the context of localized or high-dose delivery strategies.

Limitations and challenges include pre-existing antibodies to AAV capsids, potential immune responses to vector or transgene, manufacturing scale and quality control, and the limited payload capacity of about 4.7 kb, which influences promoter and transgene design.