Ribozyme with tRNA synthetase activity and methods of manufacturing and using the same

US10793858B2 · kind B2 · utility

Assignees

• Purdue Research Foundation · US
• The Regents of the University of California · US

Inventors

• Barbara L. Golden · West Lafayette, US
• Ji Chen · San Francisco, US
• Andrej Luptak · Irvine, US
• Rui Gan · Evanston, US

Key dates

• Filing date: Oct 30, 2018
• Grant date: Oct 6, 2020
• Expiry date: Jan 26, 2039

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2310/12
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

Ribozymes exhibiting tRNA synthetase activity and substrate specificity, as well as methods for engineering and producing the same, are disclosed. The ribozymes of the present disclosure comprise a T-box module fused with a flexizyme module. The flexizyme module provides high promiscuity with respect to amino acid substrates and the T-box module provides tRNA substrate specificity, which may be engineered as desired. Systems are also described for aminoacylation of suppressor tRNAs with unnatural amino acids (uAAs), such systems comprising the ribozyme previously mentioned, suppressor tRNA, and the desired uAA(s). Methods for incorporating a uAA into a growing polypeptide chain using the ribozyme hereof are also provided.