AAV Delivery

AAV Delivery uses recombinant adeno-associated virus vectors to transport therapeutic genes or genome editing components into target cells with high efficiency and a favorable safety profile ¹.

How It Works

Adeno-associated viruses are small, non-enveloped, single-stranded DNA viruses that naturally infect humans without causing disease. Recombinant AAV (rAAV) vectors replace the viral coding sequences with a therapeutic transgene cassette flanked by inverted terminal repeats (ITRs), which are the only cis-acting viral elements required for packaging and expression.

Different AAV serotypes (AAV1 through AAV13 and engineered variants) exhibit distinct tissue tropisms determined by their capsid proteins. AAV9 crosses the blood-brain barrier, AAV8 efficiently transduces hepatocytes, and AAV2 targets retinal cells. This natural tropism diversity, combined with engineered capsid variants, enables tissue-specific gene delivery for diverse therapeutic applications.

The primary limitation is the packaging capacity of approximately 4.7 kilobases, which constrains the size of deliverable transgenes. This is particularly challenging for CRISPR-Cas9 delivery, as the SpCas9 coding sequence alone occupies most of the capacity. Dual-AAV strategies and smaller Cas orthologs (SaCas9, CjCas9) address this constraint. AAV vectors predominantly remain episomal in transduced cells, providing durable expression in post-mitotic tissues ¹.

Computational Considerations

Machine learning approaches engineer novel AAV capsids with enhanced tropism, reduced immunogenicity, and improved manufacturing yield. Phylogenetic reconstruction of ancestral AAV sequences and structure-guided design produce synthetic capsids with properties not found in natural serotypes ².

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