Agilent Technologies, Inc.

Leland Stanford Junior University

University and Agilent Technologies, Inc.

Robert Kaiser

Daniel E Ryan

Douglas J Dellinger

Joel Myerson

Matthew Hebden Porteus

Rasmus O Bak

Ayal Hendel

Joe Clark

Jeffrey Robert Sampson

Provided herein are compositions and methods for inducing CRISPR/Cas-based editing of a target nucleic acid (e.g., target DNA or target RNA) in vitro or in a cell, using modified prime editing guide RNAs (pegRNAs) that incorporate one or more chemically-modified nucleotides. The modified pegRNAs disclosed herein may be used to induce Cas-mediated incorporation of one or more nucleotide changes and/or targeted mutagenesis of a target nucleic acid. The nucleotide change can include, e.g., one or more nucleotide changes, an insertion of one or more nucleotides, or a deletion of one or more nucleotides.

Guide RNAs with chemical modification for prime editing

Provided herein are methods for inducing CRISPR/Cas-based gene regulation (e.g., genome editing or gene expression) of a target nucleic acid (e.g., target DNA or target RNA) in a cell. The methods include using modified single guide RNAs (sgRNAs) that enhance gene regulation of the target nucleic acid in a primary cell for use in ex vivo therapy or in a cell in a subject for use in in vivo therapy. Additionally, provided herein are methods for preventing or treating a genetic disease in a subject by administering a sufficient amount of a modified sgRNA to correct a mutation in a target gene associated with the genetic disease.

Compositions comprising chemically modified guide RNAs for CRISPR/Cas-mediated editing of HBB

Chemically modified guide RNAS for CRISPR/Cas-mediated gene regulation

Chemically modified guide RNAs for CRISPR/CAS-mediated gene regulation

The present invention relates to modified guide RNAs and their use in clustered, regularly interspaced, short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems.

Guide RNA with chemical modifications

Growing community of inventors

Santa Clara, CA, United States of America

Robert Kaiser