Pre-existing adaptive immunity to the RNA-editing enzyme Cas13d in humans.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 35668177.
- Also identified by DOI 10.1038/s41591-022-01848-6 and PMC identifier 9307479.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
RNA-guided RNA-targeting nucleases, such as CRISPR-Cas13 proteins, have therapeutic potential for gene editing. Among Cas13d enzymes, Cas13d from the bacteria Ruminococcus flavefaciens (RfxCas13d) is of particular interest owing to its small size and high specificity. However, the existence of pre-existing immunity against RfxCas13d is unclear. In this study, we evaluated antibody and T cell responses to RfxCas13d in healthy donors using ELISA and T cell culture assays. We found RfxCas13d-reactive antibodies and CD4 and CD8 T cell responses in most donors, comparable to responses against Cas9 proteins from Staphylococcus aureus (SaCas9) and Streptococcus pyogenes (SpCas9). RfxCas13d-responding T cells could produce the inflammatory cytokines IFN-γ, TNF-α and IL-17. These findings should be taken into consideration in the development of RfxCas13d for therapy.
Medical subject headings
- CRISPR-Associated Protein 9
- CRISPR-Cas Systems