Antisense modulation of P38 mitogen activated protein kinase expression

DETAILED DESCRIPTION OF THE INVENTION p38 MAPKs play an important role in signal transduction in response to cytokines, growth factors and other cellular stimuli.
Specific responses elicited by p38 include inflammatory and apoptotic responses.
Modulation of p38 may be useful in the treatment of inflammatory diseases, such as rheumatoid arthritis.
The present invention employs antisense compounds, particularly oligonucleotides, for use in modulating the function of nucleic acid molecules encoding a p38 MAPK, ultimately modulating the amount of a p38 MAPK produced.
This is accomplished by providing oligonucleotides which specifically hybridize with nucleic acids, preferably mRNA, encoding a p38 MAPK.
The antisense compounds may be used to modulate the function of a particular p38 MAPK isoform, e.
g.
for research purposes to determine the role of a particular isoform in a normal or disease process, or to treat a disease or condition that may be associated with a particular isoform.
It may also be desirable to target multiple p38 MAPK isoforms.
In each case, antisense compounds can be designed by taking advantage of sequence homology between the various isoforms.
If an antisense compound to a particular isoform is desired, then the antisense compound is designed to a unique region in the desired isoform's gene sequence.
With such a compound, it is desirable that this compound does not inhibit the expression of other isoforms.
Less desirable, but acceptable, are compounds that do not substantially inhibit other isoforms.
By "substantially", it is intended that these compounds do not inhibit the expression of other isoforms greater than 25%; more preferred are compounds that do not inhibit other isoforms greater than 10%.
If an antisense compound is desired to target multiple p38 isoforms, then regions of significant homology between the isoforms can be used.
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"