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DNA-guided CRISPR/Cas12 for RNA targeting

Orosco, C.; Rananaware, S. R.; Huang, B.; Hanna, M. P.; Ahmadimashhadi, M. R.; Lewis, J. G.; Baugh, M. P.; Bodin, A. P.; Flannery, S. J.; Lange, I. H.; Fang, Z. R.; Karalkar, V. N.; Meister, K. S.; Jain, P. K.

2024-11-22 genetic and genomic medicine
10.1101/2024.11.21.24317744 medRxiv
Show abstract

CRISPR-Cas nucleases are transforming genome editing, RNA editing, and diagnostics but have been limited to RNA-guided systems. We present {Psi}DNA, a DNA-based guide for Cas12 enzymes, engineered for specific and efficient RNA targeting. {Psi}DNA mimics a crRNA but with a reverse orientation, enabling stable Cas12-RNA assembly and activating trans-cleavage without RNA components. {Psi}DNAs are effective in sensing short and long RNAs and demonstrated 100% accuracy for detecting HCV RNA in clinical samples. We discovered that {Psi}DNAs can guide certain Cas12 enzymes for RNA targeting in cells, enhancing mRNA degradation via ribosome stalling and enabling multiplex knockdown of multiple RNA transcripts. This study establishes {Psi}DNA as a robust alternative to RNA guides, augmenting the potential of CRISPR-Cas12 for diagnostic applications and targeted RNA modulation in cellular environments.

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"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.