Compositions and methods for performing reverse gene therapy

Abstract

The invention relates to compositions and methods for reverse gene therapy, wherein a gene therapy vector encoding a gene product (e.g. a protein) which is usually only expressed in cells of an abnormal tissue is delivered to a cell of an animal afflicted with a disease or disorder to alleviate the disease or disorder. In one embodiment, a plasmid vector encoding HERG (A561V) protein is delivered to a cell of an animal afflicted with re-entrant atrial flutter-mediated cardiac arrhythmia.

Description

[0001]This application is a continuation-in-part application of U.S. patent application Ser. No. 09 / 487,851, filed Jan. 19, 1999, and also claims priority to U.S. Provisional 60 / 374,840 filed Apr. 24, 2002, the entire disclosures of each being incorporated by reference herein.STATEMENT REGARDING FEDERALLY SUPPORTED RESEARCH AND DEVELOPMENT[0002]Pursuant to 35 U.S.C. §202(c) it is acknowledged that the U.S. Government has certain rights in the invention described herein, which was made in part with funds from the National Heart, Lung and Blood Institute, Grant number HL41663.FIELD OF THE INVENTION[0003]The present invention relates to the fields of medicine and gene therapy. More specifically, the present invention relates to an adaptation of gene therapy to the field of tissue engineering. In particular, the invention concerns the use of cells that can generate tissue in vivo (“progenitor cells”) as the means for effecting so-called reverse gene therapy (RGT), an approach generally ...

AI Technical Summary

Benefits of technology

This approach effectively alleviates diseases by expressing therapeutic genes only in affected tissues, reducing immune responses and long-term relief from symptoms, with potential for enduring benefits by using progenitor cells to establish tissues counteracting pathological conditions.

Problems solved by technology

However, virus vectors sometimes elicit an immune response in the gene therapy host, which can inhibit the therapeutic benefit provided by the vector.

Furthermore, use of retrovirus vectors can result in integration of the nucleic acid of the vector into the genome of the host, potentially causing harmful mutations.

‘Naked’ nucleic acid vectors, such as linear DNA vectors and plasmids, do not generally induce an immune response or integrate into the host genome, but are taken up and expressed by host cells less effectively than virus vectors.

Among the shortcomings of current gene therapy strategies, including both ex vivo and in vivo gene therapy methods, is a dearth of appropriate nucleic acids for delivery to diseased or otherwise abnormal cells.

Although these nucleic acids may be effective in certain instances, a serious need remains for additional nucleic acids and compositions comprising the same which, when delivered to diseased or abnormal cells, alleviate, prevent, or reverse the disease or abnormality.

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