Recent work both at the bench and the bedside demonstrate zinc-finger nucleases (ZFNs),
CRISPR/Cas9, and other programmable site-specific endonuclease technologies are being successfully
utilized within and alongside AAV vectors to induce therapeutically relevant levels of directed gene
editing within the human chromosome. Studies from past decades acknowledge that AAV vector genomes
are enhanced substrates for homology-directed repair in the presence or absence of targeted
DNA damage within the host genome. Additionally, AAV vectors are currently the most efficient format
for in vivo gene delivery with no vector related complications in >100 clinical trials for diverse
diseases. At the same time, advancements in the design of custom-engineered site-specific endonucleases and the utilization
of elucidated endonuclease formats have resulted in efficient and facile genetic engineering for basic science and for
clinical therapies. AAV vectors and gene editing technologies are an obvious marriage, using AAV for the delivery of repair
substrate and/or a gene encoding a designer endonuclease; however, while efficient delivery and enhanced gene targeting
by vector genomes are advantageous, other attributes of AAV vectors are less desirable for gene editing technologies.
This review summarizes the various roles that AAV vectors play in gene editing technologies and provides insight
into its trending applications for the treatment of genetic diseases.
Keywords: AAV Vectorization, DSB, CRISPR/Cas9, DNA, ZFNs.
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