Splice switch oligomers for TNF superfamily receptors and their use in treatment of disease
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United States of America Patent
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Nov 10, 2006
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Nov 10, 2005
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Abstract
Methods and compositions are disclosed for controlling expression of TNF receptors (TNFR1 and TNFR2) and of other receptors in the TNFR superfamily using compounds that modulate splicing of pre-mRNA encoding these receptors. More specifically these compounds cause the removal of the transmembrane domains of these receptors and produce soluble forms of the receptor which act as an antagonist to reduce TNF-.alpha. activity or activity of the relevant ligand. Reducing TNF-.alpha. activity provides a method of treating or ameliorating inflammatory diseases or conditions associated with TNF-.alpha. activity. Similarly, diseases associated with other ligands can be treated in like manner. In particular, the compounds of the invention are splice-splice switching oligomers (SSOs) which are small molecules that are stable in vivo, hybridize to the RNA in a sequence specific manner and, in conjunction with their target, are not degraded by RNAse H.
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