IL-34 Antisense Oligonucleotides for Inflammatory Disease Relief
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Solution Overview
Problem
Current treatments for inflammatory disorders such as rheumatoid arthritis, osteoarthritis, and inflammatory bowel disease lack effective and long-lasting relief, often accompanied by side effects and cycles of inflammation and remission.
Innovation Solution
Development of polynucleotides complementary to IL-34, specifically chemically modified antisense oligonucleotides and siRNAs, which are administered to inhibit IL-34 mediated inflammatory responses and cytokine production, thereby reducing inflammation and fibrosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Duration of action of moving object
If current treatments for inflammatory disorders are used, then inflammation can be temporarily suppressed, but the relief is not long-lasting and cycles of inflammation and remission occur
Solution Approach 1:
The patent employs chemically modified nucleosides (2′-O-(2-methoxyethyl) nucleosides) and modified internucleoside linkages (phosphorothioate, phosphorodithioate, phosphotriester, alkylphosphonate, aminoalkylphosphotriester, phosphoramidate, and aminoalkylphosphoramidate linkages) to alter the pharmacokinetic parameters of the antisense oligonucleotides. These chemical modifications enhance nuclease resistance, improve cellular uptake, and extend the half-life of the therapeutic agent, thereby providing long-lasting relief from inflammatory disorders without cycles of inflammation and remission
2Reliability
If current treatments for inflammatory disorders are used, then some symptom relief can be achieved, but side effects occur
Solution Approach 1:
The patent uses chemically modified nucleosides and linkages to create regions of different properties within the oligonucleotide structure. The 2′-O-(2-methoxyethyl) nucleoside modifications at specific positions enhance binding affinity and specificity to the target mRNA, while phosphorothioate and other modified linkages provide nuclease resistance and improved pharmacokinetics. This localized optimization of different regions reduces off-target effects and improves safety while maintaining therapeutic effectiveness
3Duration of action of moving object
If chemically modified antisense oligonucleotides with multiple modified nucleosides and linkages are used, then long-lasting relief from inflammatory disorders is achieved, but the complexity of the molecule increases
Solution Approach 1:
The patent divides the oligonucleotide into distinct functional regions: 2′-O-(2-methoxyethyl) nucleoside modifications at specific positions for enhanced binding and stability, and modified internucleoside linkages (phosphorothioate, phosphorodithioate, etc.) for nuclease resistance. This segmentation of functional elements allows systematic optimization of different properties while maintaining a manageable overall structure that can be synthesized and characterized
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The use of IL-34 complementary polynucleotides effectively reduces inflammatory cytokine production and IL-34 mediated responses, providing potential long-lasting relief from inflammatory disorders with minimal side effects.
Implementation Method 1
polynucleotides complementary to IL-34, specifically chemically modified antisense oligonucleotides and siRNAs, which are administered to inhibit IL-34 mediated inflammatory responses
Data Source
AI summary
Disclosed herein polynucleotides complementary to IL-34, including IL-34 antisense oligonucleotides and IL-34 siRNAs, and methods for treating inflammatory diseases, such as an inflammatory bowel disease, and/or fibrosis, associated with elevated activity or expression of IL-34. Also disclosed are pharmaceutical compositions containing a polynucleotide complementary to IL-34, for example, an IL-34 antisense oligonucleotide or an IL-34 siRNA, useful for treating inflammatory diseases and/or fibrosis and manufacture of medicaments containing a disclosed polynucleotide to be used in treating inflammatory diseases and/or fibrosis.