Title | Investigation of Cas9 antibodies in the human eye. |
Publication Type | Journal Article |
Year of Publication | 2022 |
Authors | Toral, Marcus A., Charlesworth Carsten T., Ng Benjamin, Chemudupati Teja, Homma Shota, Nakauchi Hiromitsu, Bassuk Alexander G., Porteus Matthew H., and Mahajan Vinit B. |
Journal | Nat Commun |
Volume | 13 |
Issue | 1 |
Pagination | 1053 |
Date Published | 2022 02 25 |
ISSN | 2041-1723 |
Keywords | Animals, Antibodies, CRISPR-Associated Protein 9, CRISPR-Cas Systems, Humans, Mice, Streptococcus pyogenes, T-Lymphocytes |
Abstract | 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. |
DOI | 10.1038/s41467-022-28674-1 |
Alternate Journal | Nat Commun |
PubMed ID | 35217666 |
PubMed Central ID | PMC8881612 |
Grant List | P30 EY026877 / EY / NEI NIH HHS / United States T32 GM139776 / GM / NIGMS NIH HHS / United States R01 EY030151 / EY / NEI NIH HHS / United States R01 EY024698 / EY / NEI NIH HHS / United States T32 GM007337 / GM / NIGMS NIH HHS / United States R01 EY031952 / EY / NEI NIH HHS / United States R01 EY025225 / EY / NEI NIH HHS / United States |