新加坡国立大学Gene W. Yeo团队近期取得重要工作进展，他们研究发现人类对RNA编辑酶Cas13d预先存在的适应性免疫力。相关论文2022年6月6日在线发表于《自然—医学》杂志上。

在本研究中，研究人员使用ELISA和T细胞培养试验评估了健康供体对RfxCas13d的抗体和T细胞反应。他们在大多数供体中发现了RfxCas13d反应性抗体和CD4和CD8 T细胞反应，与对来自金黄色葡萄球菌（SaCas9）和化脓性链球菌（SpCas9）的Cas9蛋白的反应类似。响应RfxCas13d的T细胞可以产生炎性细胞因子IFN-γ、TNF-α和IL-17。在开发用于治疗的RfxCas13d时应考虑这些发现。

据介绍，RNA引导的RNA靶向核酸酶，如CRISPR–Cas13蛋白，具有基因编辑的治疗潜力。 在Cas13d酶中，来自反刍球菌（Ruminococcus flavefaciens）的RfxCas13d由于其小尺寸和高特异性而受到特别关注。然而，是否存在针对RfxCas13d的预先免疫力尚不清楚。 

附：英文原文

Title: Pre-existing adaptive immunity to the RNA-editing enzyme Cas13d in humans

Author: Tang, Xin-Zi Emily, Tan, Shu Xuan, Hoon, Shawn, Yeo, Gene W.

Issue&Volume: 2022-06-06

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 CD4and CD8T 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.

DOI: 10.1038/s41591-022-01848-6

Source: https://www.nature.com/articles/s41591-022-01848-6