Compositions and methods for the treatment of hemoglobinopathies

US10619140B2 · kind B2 · utility

Assignee

• Fred Hutchinson Cancer Research Center · US

Inventors

• Ryo Takeuchi · Cambridge, US
• Mark T. Groudine · Seattle, US
• Barry L. Stoddard · Seattle, US
• Michael Bender · Osterode, DE

Key dates

• Filing date: Mar 16, 2017
• Grant date: Apr 14, 2020
• Expiry date: Mar 16, 2037

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07K2319/80
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

Provided are compositions and methods for the treatment of hemoglobinopathies such as thalassemias and sickle cell disease. Compositions and methods include one or more endonuclease(s) or endonuclease fusion protein(s), including one or more homing endonuclease(s) and/or homing endonuclease fusion protein(s) and/or CRISPR endonuclease(s) and/or CRISPR endonuclease fusion protein(s): (a) to disrupt a Bcl11a coding region; (b) to disrupt a Bcl11a gene regulatory region; (c) to modify an adult human β-globin locus; (d) to disrupt a HbF silencing DNA regulatory element or pathway, such as a Bcl11a-regulated HbF silencing region; (e) to mutate one or more γ-globin gene promoter(s) to achieve increased expression of a γ-globin gene; (f) to mutate one or more δ-globin gene promoter(s) to achieve increased expression of a δ-globin gene; and/or (g) to correct one or more β-globin gene mutation(s).