Compositions and methods for self-regulated inducible gene expression

US10392622B2 · kind B2 · utility

Assignee

• The Trustees of the University of Pennsylvania · US

Inventors

• Mitchell Lee Lewis · Cairns, AU
• Jean Bennett · Via Enrico Fermi, US
• Luk E. Vandenberghe · Weston, US
• Matthew Sochor · Watertown, US
• Theodore G. Drivas · Philadelphia, US

Key dates

• Filing date: Jul 31, 2015
• Grant date: Aug 27, 2019
• Expiry date: Jul 31, 2035

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2830/52
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

A self-regulating gene expression construct comprises a single promoter in operative association with a repressor sequence (e.g., bacterial repressor lacI or gaiR), operator sequence(s) responsive to the expressed repressor protein, and a transgene. A dual-regulating construct comprises a single promoter controlling expression of a bacterial repressor sequence and a transgene, and which, in the presence of a first inducer molecule, transcribes the transgene and repressor; and a ribozyme in association with an aptamer sequence, the aptamer sequence capable of interacting with a second inducer molecule to terminate mRNA degradation by the ribozyme. Also provided are recombinant vectors or viruses containing the self-regulating or dual self-regulating constructs and cells containing the vectors. Such compositions are useful in methods of treating a diseases using gene therapy.