近日，美国犹他大学医学院刘洋及其课题组的研究开发出了RNA触发的CRISPR-Cas12a2细胞杀伤。相关论文发表在2026年5月6日出版的《自然》杂志上。

在这里，该研究组展示了Cas12a2，一种最近发现的V型CRISPR核酸酶，表现出RNA触发的DNA切碎，并能够编程和序列特异性地消除表达目标转录物的酵母和人类细胞。触发Cas12a2会引发反式核酸中猖獗的双链DNA断裂，导致细胞死亡。细胞杀伤可以被广泛的靶转录物激活，没有观察到脱靶激活。利用这种方法，该团队选择性地消除了含有人乳头瘤病毒的细胞、未能进行基因编辑的细胞或编码KRAS中普遍致癌点突变的细胞。这些发现扩展了CRISPR工具箱，允许基于其转录谱选择性消除真核细胞。

据悉，在基础研究、医学、生物技术和农业中，基于基因或转录特性选择性地根除靶细胞仍然很重要。对于涉及细菌的应用，CRISPR核酸酶提供了有希望的选择，因为它们能够进行RNA引导的反选择；然而，在真核生物中，将这些相同的核酸酶进行反选择被证明更具限制性。

附：英文原文

Title: RNA-triggered cell killing with CRISPR–Cas12a2

Author: Scholz, Paul, Thompson, Jared, Crosby, Kadin T., Fauth, Torsten, Krah, Nathan M., Schlauderaff, Grant, Back, Robin, Berkheimer, Zachary A., Jolley, Alivia, Sombroek, Dirk, Medert, Rebekka, Zurek, Christian, Dmytrenko, Oleg, Wilson, Emily, Schut, Friso T., Rutter, Jared, Zhang, Xiaoyang, Krohn, Michael, Jackson, Ryan N., Beisel, Chase L., Liu, Yang

Issue&Volume: 2026-05-06

Abstract: Selectively eradicating target cells on the basis of their genetic or transcriptional identity remains important in basic research, medicine, biotechnology and agriculture1,2,3. For applications involving bacteria, CRISPR nucleases offer promising options due to their ability to enact RNA-guided counterselection4,5,6,7; however, using these same nucleases for counterselection in eukaryotes has proven much more restrictive8,9,10,11,12,13,14. Here we show that Cas12a2, a recently discovered type V CRISPR nuclease, exhibits RNA-triggered DNA shredding15,16, and enables programmable and sequence-specific elimination of yeast and human cells expressing a target transcript. Triggering Cas12a2 elicits rampant double-stranded DNA breaks in trans, leading to cell death. Cell killing can be activated by a wide range of target transcripts, with no observed off-target activation. Leveraging this approach, we selectively eliminate cells that harbour human papillomavirus, cells that failed to undergo gene editing, or cells that encode a prevalent oncogenic point mutation in KRAS. These findings expand the CRISPR toolbox to allow the selective elimination of eukaryotic cells on the basis of their transcriptional profile.

DOI: 10.1038/s41586-026-10466-y

Source: https://www.nature.com/articles/s41586-026-10466-y