Expression of apoAI and variants thereof using spliceosome mediated RNA trans-splicing

US8883753B2 · kind B2 · utility

Assignee

• Virxsys Corporation · US

Inventors

• Madaiah Puttaraju · Germantown, US
• Edward Otto · Reston, US
• Mariano A. Garcia-Blanco · Hillsborough, US
• Gerard J. McGarrity · Gaithersburg, US
• Gary Temple · Washington Grove, US

Key dates

• Filing date: Jun 22, 2011
• Grant date: Nov 11, 2014
• Expiry date: Jul 22, 2031

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C12N2320/33
• WIPO field: Biotechnology
• WIPO sector: Chemistry

Abstract

Methods and compositions for generating novel nucleic acid molecules through targeted spliceosome mediated RNA trans-splicing that result in expression of a apoAI protein, an apoAI variant, the preferred embodiment referred to herein as the apoAI Milano variant, a pre-pro-apoAI or an analog of apoAI. The methods and compositions include pre-trans-splicing molecules (PTMs) designed to interact with a target precursor messenger RNA molecule (target pre-mRNA) and mediate a trans-splicing reaction resulting in the generation of a novel chimeric RNA molecule (chimeric RNA) capable of encoding apoAI, the apoAI Milano variant, or an analog of apoAI. The expression of this apoAI protein results in protection against vascular disorders resulting from plaque build up, i.e., atherosclerosis, strokes and heart attacks.