Therapeutic use of cis-element decoys in vivo

Abstract

The invention provides for the use of oligodeoxynucleotide decoys for the prophylactic or therapeutic treatment of diseases associated with the binding of endogenous transcription factors to genes involved in cell growth, differentiation and signaling or to viral genes. By inhibiting endogenous trans-activating factors from binding transcription regulatory regions, the decoys modulate gene expression and thereby regulating pathological processes including inflammation, intimal hyperplasia, angiogenesis, neoplasia, immune responses and viral infection. The decoys are administered in amounts and under conditions whereby binding of the endogenous transcription factor to the endogenous gene is effectively competitively inhibited without significant host toxicity. The subject compositions comprise the decoy molecules in a context which provides for pharmacokinetics sufficient for effective therapeutic use.

Description

INTRODUCTION[0001] 1. Technical Field[0002] The field of this invention is therapeutic treatment of disease with double stranded nucleic acids which bind transcription factors.[0003] 2. Background[0004] A wide variety of diseases result from the over- or under-expression of one or more genes. Given cells may make insufficient amounts of a protein (e.g. insulin) or too much of a protein, be it a normal protein (e.g. TNF), a mutant protein (e.g. an oncogene), or a non-host protein (e.g. HIV tat). The ultimate goal of therapeutic intervention in such diseases is a selective modulation of gene expression.[0005] A variety of methods of transcriptional modulation in vitro have been reported including the use of anti-sense nucleic acids capable of binding nascent message, intracellular immunization with dominant negative mutants.[0006] With the broad potential therapeutic applications, massive efforts have been extended by prominent laboratories and clinics around the world to extend these...

AI Technical Summary

Benefits of technology

0011] The methods comprise administering to a patient double stranded nucleic acid "decoys" in a form such that the decoys are capable of entering target cells of the patient and specifically binding an endogenous transcription factor, thereby competitively inhibiting the transcription factor from binding to an endogenous gene. The decoys are administered in amounts and under conditions where

Problems solved by technology

To date, the transcription factor decoy strategy has never been successfully adopted in vivo.

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