Innovative Genomics Institute

A noncontiguous code for RNA-guided DNA recognition at the origin of CRISPR-Cas

CRISPR-Cas provides RNA-mediated adaptive immunity, but how its first RNA-guided effector arose is unclear. In this study, we report the discovery of Viral Interference Programmable Repeat (VIPR) systems consisting of a Vipr protein ancestral to the earliest CRISPR-Cas effectors...

VIPR RNA-guided DNA recognition by noncontiguous geometric triplex formation

Viral interference programmable repeat (VIPR) systems use a noncontiguous code for RNA-guided transcriptional silencing. How the Vipr protein and a VIPR RNA (vrRNA) comprising alternating GGY and NN segments achieve precise DNA targeting is unknown. Here, we present 21 cryo–elect...

Engineered Orthogonal Translation Systems from Metagenomic Libraries Expand the Genetic Code

Abstract Genetic code expansion with noncanonical amino acids (ncAAs) opens new opportunities for the design and engineering of proteins by broadening their chemical repertoire. Unfortunately, ncAA incorporation into proteins is limited both by a small collection of orthogonal am...

Predicting genome-wide functional constraints with GPN-Star

Abstract Genomic language models have emerged as a powerful approach for learning genome-wide functional constraints directly from DNA sequences 1 . However, standard genomic language models adapted from natural language processing often require large model sizes and computationa...