Gene correction of Pompe disease and other autosomal recessive disorders via RNA-guided nucleases

US11739320B2 · kind B2 · utility

Assignee

• Wisconsin Alumni Research Foundation · US

Inventors

• Krishanu Saha · Middleton, US
• Jared Matthew Carlson-Stevermer · Burlingame, US
• Lucille Katherine Kohlenberg · Elm Grove, US

Key dates

• Filing date: Nov 5, 2019
• Grant date: Aug 29, 2023
• Expiry date: Dec 13, 2041

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2800/80
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Described herein are guide RNAs and modified guide RNAs suitable for biallelic correction of Pompe disease. Also included are methods of modifying a target gene in a patient or in a patient-derived cell, wherein the patient has an autosomal recessive disorder with compound heterozygous mutations, the methods including delivering a first modified guide RNA, a second modified guide RNA, a Cas9 polypeptide, a biotin-binding molecule, a first biotinylated donor polynucleotide, and a second biotinylated donor polynucleotide. The first modified guide RNA and the first biotinylated donor polynucleotide correct a first diseased allele, and the second modified guide RNA and the second biotinylated donor polynucleotide correct a second diseased allele.