Year: 2022
Type: article
Study design: Observational Study
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.
Source: Nature Communications
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $5,890
Awards: G1685131131, Proteomic Biomarkers of Intraocular Infection, G2388168824, G2911450482, Mechanism-based therapies for photoreceptor degeneration, G4570518681, Graduate Research Fellowship Program (GRFP), G6294697701, G6421867929, G6661425536, G6902378652, G7118691020, G8137220643, Inflammatory Gene Transcription in the Retina, Medical Scientist Training Program, G8658418346, Medical Scientist Training Program, Stanford Vision Research Core, Gene Editing and Silencing in Phototransduction
OpenAlex ID: W4214628568