Journal article
Investigation of Cas9 antibodies in the human eye
Nature communications, Vol.13(1), pp.1053-1053
02/25/2022
DOI: 10.1038/s41467-022-28674-1
PMCID: PMC8881612
PMID: 35217666
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.
Details
- Title: Subtitle
- Investigation of Cas9 antibodies in the human eye
- Creators
- Marcus A Toral - Medical Scientist Training Program and Graduate Program in Molecular Medicine, University of Iowa, Iowa City, IA, USACarsten T Charlesworth - Department of Pediatrics, Stanford University, Palo Alto, CA, USABenjamin Ng - Medical Sciences Division, University of Oxford, Oxford, UKTeja Chemudupati - Molecular Surgery Program, Department of Ophthalmology, Byers Eye Institute, Stanford University, Palo Alto, CA, USAShota Homma - Department of Genetics, Stanford University, Palo Alto, CA, USAHiromitsu Nakauchi - Division of Stem Cell Therapy, Distinguished Professor Unit, Institute of Medical Science, University of Tokyo, Tokyo, JapanAlexander G Bassuk - Departments of Pediatrics and Neurology and The Iowa Neuroscience Institute (INI), University of Iowa, Iowa City, IA, USAMatthew H Porteus - Department of Pediatrics, Stanford University, Palo Alto, CA, USA. mporteus@stanford.eduVinit B Mahajan - Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, Palo Alto, CA, USA. vinit.mahajan@stanford.edu
- Resource Type
- Journal article
- Publication Details
- Nature communications, Vol.13(1), pp.1053-1053
- DOI
- 10.1038/s41467-022-28674-1
- PMID
- 35217666
- PMCID
- PMC8881612
- NLM abbreviation
- Nat Commun
- eISSN
- 2041-1723
- Grant note
- P30EY026877 / U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) R01EY031952 / U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) R01EY030151 / U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) R01EY025225 / U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI) R01EY024698 / U.S. Department of Health & Human Services | NIH | National Eye Institute (NEI)
- Language
- English
- Date published
- 02/25/2022
- Academic Unit
- Neurology; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Neurology (Pediatrics)
- Record Identifier
- 9984222805502771
Metrics
12 Record Views