Our AI-guided design of RNA-guided nucleases is now out in @science.org 💻🧬 We used structure and evolutionary data to generate minimal, active and divergent gene editors! www.science.org/doi/10.1126/... Congrats to @petrskopintsev.bsky.social @isabelesain.bsky.social @evandeturk.bsky.social & team!

Structure and evolution-guided design of minimal RNA-guided nucleases

The design of RNA-guided nucleases with properties not limited by evolution can expand programmable genome-editing capabilities. However, generating diverse multidomain proteins with robust enzymatic ...

science.org

The wobble-skip mechanism of matching two-of-three bases is wildly cool. Most synonymous mutants can’t escape

Kenneth Loi@kenjmloi.bsky.social · 3mo ago

Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR. We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets. Thread + link below.

We present VIPR, a phage-encoded RNA-guided system that recognizes DNA with a noncontiguous code unlike CRISPR. Tiny, programmable, possibly ancestral to CRISPR immunity; VIPR is built around a striking RNA-DNA-DNA triplex.

Kenneth Loi@kenjmloi.bsky.social · 3mo ago

Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR. We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets. Thread + link below.

Excited to share our discovery of a new programmable RNA-guided DNA-targeting system hiding inside bacteriophages that predates CRISPR. We call it VIPR (Viral Interference Programmable Repeat), and it uses an entirely new logic to find its targets. Thread + link below.

Now online at @nature.com we show how the Panoptes defense system protects against viruses that attempt immune evasion - and expands our understanding of the role of oligonucleotides in immunity. Check out this work co-led with @benadler.bsky.social here: www.nature.com/articles/s41...

A miniature CRISPR–Cas10 enzyme confers immunity by inhibitory signalling - Nature

Panoptes, an anti-phage defence system against virus-mediated immune suppression, is revealed.

nature.com

AFESM: a metagenomic guide through the protein structure universe! We clustered 821M structures (AFDB&ESMatlas) into 5.12M groups; revealing biome-specific groups, only 1 new fold even after AlphaFold2 re-prediction & many novel domain combos. 🧵 🌐 afesm.foldseek.com 📄 www.biorxiv.org/content/10.1...

Preprint alert! ✨ In this project that I co-led with @benadler.bsky.social, we show that a miniature CRISPR-Cas10-like enzyme, mCpol, uses a novel inverse signaling mechanism to prevent the spread of viruses that attempt immune evasion by depleting host cyclic nucleotides. Check it out:

A miniature CRISPR-Cas10 enzyme confers immunity by an inverse signaling pathway

Microbial and viral co-evolution has created immunity mechanisms involving oligonucleotide signaling that share mechanistic features with human anti-viral systems. In these pathways, including CBASS a...

biorxiv.org