Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

CRISPR-Csm for eukaryotic RNA knockdown and imaging without toxicity

Targeted RNA degradation remains a challenge using existing methods owing to off-target effects and toxicity. We adapted the CRISPR-Csm complex, a multi-protein effector from type III CRISPR systems, for precise knockdown of nuclear or cytoplasmic transcripts in eukaryotic cells with minimal side effects.

This is a preview of subscription content, access via your institution

Access options

Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Fig. 1: Overview of the CRISPR-Csm system.


  1. Lennox, K. A. & Behlke, M. A. Mini-review on current strategies to knockdown long non-coding RNAs. J. Rare Dis. Res. Treat. 1, 66–70 (2016). A review article that describes the limitations of RNAi, especially for knockdown of long non-coding RNAs.

    Google Scholar 

  2. Ai, Y., Liang, D. & Wilusz, J. E. CRISPR/Cas13 effectors have differing extents of off-target effects that limit their utility in eukaryotic cells. Nucleic Acids Res. 50, e65 (2022). This paper reports the toxic side effects of Cas13’s trans-cleavage when used for RNA knockdown in eukaryotic cells.

    CAS  Google Scholar 

  3. Kolesnik, M. V. et al. Deciphering the most complex prokaryotic immune system. Biochemistry (Moscow) 86, 1301–1314 (2021). This review article summarizes the type III CRISPR immune system.

    CAS  Google Scholar 

  4. Staals, R. H. J. et al. RNA Targeting by the Type III-A CRISPR-Cas Csm Complex of Thermus thermophilus. Mol. Cell 56, 518–530 (2014). This paper characterizes the RNA targeting and cleavage activity of the Csm complex.

    CAS  Google Scholar 

Download references

Additional information

Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

This is a summary of: Colognori, D., Trinidad, M. & Doudna, J. A. Precise transcript targeting by CRISPR-Csm complexes. Nat. Biotechnol. (2023).

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

CRISPR-Csm for eukaryotic RNA knockdown and imaging without toxicity. Nat Biotechnol (2023).

Download citation

  • Published:

  • DOI:


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing