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isis 104838
- Development stage
- Phase 2
- Lead developer
- Ionis Pharmaceuticals
- Modality
- Antisense Oligonucleotides (ASOs) → Long RNA Therapeutics → RNA Therapeutics → Nucleic Acid Therapeutics, Modified DNA Oligonucleotides → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics, Single-strand DNA → Antisense DNA → DNA Therapeutics → Nucleic Acid Therapeutics
- Administration
- Intravenous, Subcutaneous, Oral
01
Overview
ISIS 104838 is a second-generation antisense oligonucleotide drug designed to inhibit the production of tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine implicated in the pathogenesis of several inflammatory diseases, including rheumatoid arthritis. The molecule is a 20-mer phosphorothioate antisense oligonucleotide with five 2'-O-methoxyethyl modifications at both the 3' and 5' ends and ten central unmodified deoxynucleotides. It binds specifically to TNF-alpha mRNA, leading to its degradation or inhibition of translation, thereby reducing TNF-alpha protein levels. Developed using proprietary chemistry by Isis Pharmaceuticals (now Ionis Pharmaceuticals), it was investigated for subcutaneous, intravenous, and oral administration. Clinical trials demonstrated significant suppression of TNF-alpha production ex vivo and supported further development for inflammatory conditions such as rheumatoid arthritis[1][3][4][5].
- Other names
- TNF-alpha inhibitor (as a synonym in some sources)
02
Targets
TNFA (Tumor necrosis factor alpha (soluble))
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