@article {1896,
	title = {Investigation of Cas9 antibodies in the human eye.},
	journal = {Nat Commun},
	volume = {13},
	year = {2022},
	month = {2022 02 25},
	pages = {1053},
	abstract = {<p>Preexisting immunity against Cas9 proteins in humans represents a safety risk for CRISPR-Cas9 technologies. However, it is unclear to what extent preexisting Cas9 immunity is relevant to the eye as it is targeted for early in vivo CRISPR-Cas9 clinical trials. While the eye lacks T-cells, it contains antibodies, cytokines, and resident immune cells. Although precise mechanisms are unclear, intraocular inflammation remains a major cause of vision loss. Here, we used immunoglobulin isotyping and ELISA platforms to profile antibodies in serum and vitreous fluid biopsies from human adult subjects and Cas9-immunized mice. We observed high prevalence of preexisting Cas9-reactive antibodies in serum but not in the eye. However, we detected intraocular antibodies reactive to S. pyogenes-derived Cas9 after S. pyogenes intraocular infection. Our data suggest that serum antibody concentration may determine whether specific intraocular antibodies develop, but preexisting immunity to Cas9 may represent a lower risk in human eyes than systemically.</p>
},
	keywords = {Animals, Antibodies, CRISPR-Associated Protein 9, CRISPR-Cas Systems, Humans, Mice, Streptococcus pyogenes, T-Lymphocytes},
	issn = {2041-1723},
	doi = {10.1038/s41467-022-28674-1},
	author = {Toral, Marcus A and Charlesworth, Carsten T and Ng, Benjamin and Chemudupati, Teja and Homma, Shota and Nakauchi, Hiromitsu and Bassuk, Alexander G and Porteus, Matthew H and Mahajan, Vinit B}
}
