Chimeric peptides for antisense delivery

US12370261B2 · kind B2 · utility

Assignees

• Sarepta Therapeutics, Inc. · US
• Massachusetts Institute of Technology · US

Inventors

• Bradley L. Pentelute · Cambridge, US
• Colin M. Fadzen · Cambridge, US
• Rebecca L. Holden · Cambridge, US
• Justin Wolfe · Lawrenceville, US
• Zi-Ning Choo · Cambridge, US
• Monica Yao · Cambridge, US
• Gunnar J. Hanson · Cambridge, US

Key dates

• Filing date: Mar 15, 2019
• Grant date: Jul 29, 2025
• Expiry date: Aug 16, 2039

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2310/3513
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Provided herein are oligonucleotides, chimeric peptides, and peptide-oligonucleotide-conjugates, the chimeric peptides and peptide-oligonucleotide-conjugates comprising at least two cell-penetrating peptides, wherein at least one of the cell-penetrating peptides is an amphipathic peptide and at least one of the cell-penetrating peptides is an oligoarginine peptide. The oligoarginine peptide comprises the sequence [(RYzR)x] (SEQ ID NOs: 15-18), wherein R is arginine, Y is independently selected from aminohexanoic acid (X) or β-alanine (B). Also provided herein are methods of treating a muscle disease, a viral infection, or a bacterial infection in a subject in need thereof, comprising administering to the subject oligonucleotides, chimeric peptides, and peptide-oligonucleotide-conjugates comprising at least two cell-penetrating peptides, wherein at least one of the cell-penetrating peptides is an amphipathic peptide and at least one of the cell-penetrating peptides is an oligoarginine peptide described herein.