Recombinant adeno-associated virus (rAAV) based genome engineering is a genome editing platform centered on the use of recombinant AAV vectors that enables insertion, deletion or substitution of DNA sequences into the genomes of live mammalian cells. The technique builds on Mario Capecchi and Oliver Smithies' Nobel Prize–winning discovery that homologous recombination (HR), a natural hi-fidelity DNA repair mechanism, can be harnessed to perform precise genome alterations in mice. rAAV mediated genome-editing improves the efficiency of this technique to permit genome engineering in any pre-established and differentiated human cell line, which, in contrast to mouse ES cells, have low rates of HR.
The technique has been widely adopted for use in engineering human cell lines to generate isogenic human disease models. It has also been used to optimize bioproducer cell lines for the biomanufacturing of protein vaccines and therapeutics. In addition, due to the non-pathogenic nature of rAAV, it has emerged as a desirable vector for performing gene therapy in live patients.