Chimera (double) decoy

Inventors

Morishita, Ryuichi • Ogihara, Toshio • Aoki, Motokuni • Miyake, Takashi

Assignees

Anges Inc

Abstract

The present invention provides a prophylactic, ameliorative or therapeutic medicament for vascular restenosis, ischemic disease, allergic disease, inflammatory disease, autoimmune disease, or cancer metastasis, invasion (cancer metastasis/invasion) or cachexia based on the inhibitory action on a plural of transcriptional regulatory factor. A chimera (double) decoy of the present invention has plural transcriptional regulatory factor binding sequences in a single molecule thereof. Thus, it is able to inhibit the activity of plural transcriptional regulatory factors with a single molecule. For example, stenosis of an anastomosed site of an artificial blood vessel is caused by thickening of the vascular intima, and this is mainly caused by activation of cell proliferation by an inflammatory reaction occurring at the anastomosed site. Thus, thickening of vessel walls can be inhibited by simultaneously inhibiting two transcriptional regulatory factors involved in inflammation and cell proliferation by using the chimera decoy of the present invention.

Core Innovation

The invention relates to a chimera (double) decoy oligonucleotide that contains a plurality of transcriptional regulatory factor binding sequences in a single double-stranded nucleic acid. The chimera decoy includes an NF-κB transcriptional regulatory factor binding sequence and an E2F transcriptional regulatory factor binding sequence within one nucleic acid construct, as represented by SEQ ID NO:1.

The invention addresses the problem of inhibiting both inflammation and cell proliferation by simultaneously using NF-κB and E2F transcriptional regulatory factor binding sequences in the same double-stranded nucleic acid. The stated objective is to treat or prevent vascular restenosis and other inflammatory/autoimmune/allergic and metastatic diseases, using the chimera decoy as a transcriptional regulatory factor decoy.

The disclosure includes specific consensus binding sequences and variants for NF-κB and E2F, a structural formula for the chimera decoy oligonucleotide, and pharmaceutical composition and medicament use. Experimental results indicate inhibition of vascular smooth muscle cell proliferation and migration and reduced neointimal thickening in a rabbit bypass model, accompanied by decreased macrophage infiltration and reduced PCNA-positive proliferating cells.

Claims Coverage

The only independent claim provided is directed to a chimera (double) decoy oligonucleotide sequence (SEQ ID NO:1) that combines two transcriptional regulatory factor binding sequences within a single double-stranded nucleic acid. It includes 2 main inventive components: an NF-κB binding sequence and an E2F binding sequence.

The inventive coverage is centered on a specific chimera (double) decoy oligonucleotide (SEQ ID NO:1) in which SEQ ID NO:1 contains both an NF-κB transcriptional regulatory factor binding sequence and an E2F transcriptional regulatory factor binding sequence.

Stated Advantages

Documented Applications