Antisense modulation of stat3 expression

DETAILED DESCRIPTION OF THE INVENTION STAT3 plays an important role in cytokine signal transduction.
Overexpression and/or constitutive activation of STAT3 is associated with a number of inflammatory diseases and cancers.
As such, this DNA-binding protein represents an attractive target for treatment of such diseases.
In particular, modulation of the expression of STAT3 may be useful for the treatment of diseases such as rheumatoid arthritis, breast cancer, brain cancer, leukemias and lymphomas.
The present invention employs antisense compounds, particularly oligonucleotides, for use in modulating the function of nucleic acid molecules encoding STAT3, ultimately modulating the amount of STAT3 produced.
This is accomplished by providing oligonucleotides which specifically hybridize with nucleic acids, preferably mRNA, encoding STAT3.
This relationship between an antisense compound such as an oligonucleotide and its complementary nucleic acid target, to which it hybridizes, is commonly referred to as "antisense".
"Targeting" an oligonucleotide to a chosen nucleic acid target, in the context of this invention, is a multistep process.
The process usually begins with identifying a nucleic acid sequence whose function is to be modulated.
This may be, as examples, a cellular gene (or mRNA made from the gene) whose expression is associated with a particular disease state, or a foreign nucleic acid from an infectious agent.
In the present invention, the targets are nucleic acids encoding STAT3; in other words, a gene encoding STAT3, or mRNA expressed from the STAT3 gene.
mRNA which encodes STAT3 is presently the preferred target.
The targeting process also includes determination of a site or sites within the nucleic acid sequence for the antisense interaction to occur such that modulation of gene expression will result.
In accordance with this invention, persons of ordinary skill in the art will understand that messenger RNA includes not only the information to encode a protein using the three letter genetic code, but also associated ribonucleotides which form a region known to such persons as the 5'-untranslated region, the 3'-untranslated region, the 5' cap region and intron/exon junction ribonucleotides