Paper walk/talk-through on articles exploring use of the CRISPR-Cas12a2 system in eukaryotic cells @thebumblingbiochemist
Paper walk/talk-through on articles exploring use of the CRISPR-Cas12a2 system in eukaryotic cells  @thebumblingbiochemist
Uploaded July 2026 | Updated September 2026, 2 weeks ago
CRISPR/Cas12a2, what’ll it do? Use an RNA guide to target and destroy specific cells for you! The term “CRISPR” typically evokes thoughts of gene editing, but there’s actually a lot of CRISPR/Cas systems, including Cas12a2 which, rather than making very specific cuts to DNA it’s guided to will chew up any DNA around it, causing cell death - but ONLY when a specific mRNA transcript it’s sent to is present. This makes it potentially useful to seek out and destroy cells containing cancer-causing mutations, virus-infected cells, cells that haven’t undergone desired gene editing, etc.

Sorry this got so long - I really went deep in this geek out, but start with a more gist-y version and perspective for folks who don’t want all the details.

Speaking of details, if you want to follow along:

Here are the 2 papers I go into

Scholz, P.; Thompson, J.; Crosby, K. T.; Fauth, T.; Krah, N. M.; Schlauderaff, G.; Back, R.; Berkheimer, Z. A.; Jolley, A.; Sombroek, D.; Medert, R.; Zurek, C.; Dmytrenko, O.; Wilson, E.; Schut, F. T.; Rutter, J.; Zhang, X.; Krohn, M.; Jackson, R. N.; Beisel, C. L.; Liu, Y. RNA-Triggered Cell Killing with CRISPR–Cas12a2. Nature 2026, 1–10. doi.org/10.1038/s41586-026-10466-y.

Zeng, J.; Cheng, Z.; Chen, H.; Wang, Z.; Thompson, J.; Crosby, K. T.; Han, H.; Singhal, A.; Ngo, W.; Xia, C.; Rosas-Rivera, D.; Zhang, Z.; Kang, M. H.; Mao, Y.; Diolaiti, M. E.; Lee, G. C.; Diffley, J. F. X.; Song, Y.; Qiu, L.; Krah, N. M.; Murthy, N.; Jackson, R. N.; Liu, Y.; Ashworth, A.; Doudna, J. A. Targeting Cancer-Specific Mutations with RNA-Triggered Chromatin Shredding. Nature 2026, 1–3. doi.org/10.1038/s41586-026-10738-7.

Preprint version that’s freely-accessible: doi.org/10.64898/2026.05.08.723607

Highlighted in this News & Views piece: Takallo, M.; Staals, R. H. J. DNA-Shredding CRISPR Enzyme Takes Aim at Cancer Cells. Nature 2026. doi.org/10.1038/d41586-026-02122-2.

Building off of these papers that showed what the Cas12a2 protein does and how - but in prokaryotic cells. The more recent papers show that it can be used in eukaryotic cells:

Dmytrenko, O.; Neumann, G. C.; Hallmark, T.; Keiser, D. J.; Crowley, V. M.; Vialetto, E.; Mougiakos, I.; Wandera, K. G.; Domgaard, H.; Weber, J.; Gaudin, T.; Metcalf, J.; Gray, B. N.; Begemann, M. B.; Jackson, R. N.; Beisel, C. L. Cas12a2 Elicits Abortive Infection through RNA-Triggered Destruction of dsDNA. Nature 2023, 613 (7944), 588–594. doi.org/10.1038/s41586-022-05559-3.

Bravo, J. P. K.; Hallmark, T.; Naegle, B.; Beisel, C. L.; Jackson, R. N.; Taylor, D. W. RNA Targeting Unleashes Indiscriminate Nuclease Activity of CRISPR–Cas12a2. Nature 2023, 613 (7944), 582–587. doi.org/10.1038/s41586-022-05560-w.

Much more on CRISPR/Cas systems and uses: bit.ly/crisprcasscience & YouTube: youtu.be/sH6525d-A4s

Hope I interpreted everything correctly, apologies for any mistakes, and thanks for letting me geek out!
     
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Paper walk/talk-through on articles exploring use of the CRISPR-Cas12a2 system in eukaryotic cells

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