Compositions and methods for transient delivery of nucleases

US10584321B2 · kind B2 · utility

Assignee

• University of Massachusetts · US

Inventors

• Guangping Gao · Rosemont, US
• Phillip D. Zamore · Marlborough, US
• Dan Wang · Beijing, CN

Key dates

• Filing date: Feb 12, 2016
• Grant date: Mar 10, 2020
• Expiry date: May 28, 2036

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2750/14143
• WIPO field: Pharmaceuticals
• WIPO sector: Chemistry

Abstract

The disclosure in some aspects relates to recombinant adeno-associated viruses having nuclease grafted to one or more capsid proteins. In some aspects, the disclosure relates to isolated AAV capsid proteins having terminally grafted nucleases and isolated nucleic acids encoding the same. Recent approaches to delivering nucleases to cells for gene editing have focused on delivering of expression vectors engineered to express the nucleases in target cells. However, these approaches have proved to be problematic in many instances due to genotoxicity resulting from to prolonged expression of gene editing system in vivo. To prevent such off-target genotoxicity due to prolonged presence of a gene editing system, several studies explored delivery of mRNA or protein instead of delivering the gene coding for the nucleases in cell culture.