AAVbased

AAVbased refers to the use of adeno-associated virus (AAV) vectors in gene delivery and therapy. AAVs are small, non-enveloped, replication-defective parvoviruses that require helper functions for replication. In a typical gene therapy vector, most of the wild-type viral genes are removed and a therapeutic transgene is inserted, leaving the inverted terminal repeats (ITRs) that are essential for replication and packaging. The choice of capsid serotype (for example, AAV2, AAV8, AAV9, and others) largely determines tissue tropism and transduction efficiency.

Recombinant AAV (rAAV) vectors are designed so the transgene expression is driven by a promoter of choice and delivered as an episomal DNA form. AAV vectors can provide long-term transgene expression in non-dividing cells, with expression often persisting for years in tissues such as muscle, retina, and the liver. The maximum payload is typically around 4.7 kilobases, which constrains the size of therapeutic genes and regulatory elements that can be delivered.

Manufacturing of AAV-based therapies usually involves plasmid-based or cell-based production using producer cells (commonly HEK293) and purification processes to obtain clinical-grade vectors. Clinical and commercial AAV therapies have gained approval for ocular, hepatic, and neuromuscular diseases, such as Luxturna for RPE65-related retinal dystrophy and Zolgensma for spinal muscular atrophy (AAV9-based).

Challenges include pre-existing neutralizing antibodies that can limit re-dosing, limited cargo capacity, complex manufacturing, and potential immune responses. Safety profiles are generally favorable but can be dose- and serotype-dependent, with rare events such as hepatotoxicity or inflammatory reactions reported in some contexts. Ongoing research aims to expand cargo capacity, improve tissue targeting with engineered capsids, and reduce immunogenicity.