Modified Oligonucleotides Targeting Notch Pathway for Respiratory Mucus Reduction
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Solution Overview
Problem
Current treatments for respiratory disorders associated with excessive mucus production, such as asthma, COPD, IPF, and CF, are inadequate in effectively modulating the Notch signaling pathway to reduce mucus production and improve lung function.
Innovation Solution
The use of modified oligonucleotides complementary to Notch signaling pathway transcripts, specifically targeting Notch1, Notch2, Notch3, Notch4, JAG1, JAG2, DLL1, DLL3, DLL4, or Hes-1, to inhibit the expression or activity of these pathways, thereby reducing mucus production and enhancing trans-differentiation from club cells to ciliated cells, leading to improved lung function.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional treatments are used for respiratory disorders, then general symptom management is achieved, but effective modulation of the Notch signaling pathway to reduce mucus production is not achieved
Solution Approach 1:
The patent extracts and targets the specific Notch signaling pathway as the source of excessive mucus production. By using modified oligonucleotides that specifically bind to Notch pathway transcripts (Notch1, Notch2, Notch3, Notch4, JAG1, JAG2, DLL1, DLL3, DLL4, or Hes-1), the invention isolates and inhibits this particular signaling pathway while leaving other physiological functions intact, thereby reducing mucus production without broad suppressive effects
Solution Approach 2:
The patent changes the molecular parameters of the treatment by using chemically modified oligonucleotides with enhanced stability and specificity. These modified oligonucleotides alter the pharmacokinetic and pharmacodynamic parameters of Notch pathway inhibition, achieving more reliable and sustained reduction of mucus production compared to conventional treatments
2Reliability
If modified oligonucleotides are used to inhibit Notch signaling pathway, then mucus production is reduced and lung function is improved, but treatment complexity increases
Solution Approach 1:
The patent introduces modified oligonucleotides as intermediary molecules that mediate between the administered treatment and the Notch signaling pathway. These oligonucleotides serve as specific mediators that bind to target transcripts and inhibit translation, providing a controlled and specific mechanism to improve lung function while managing treatment complexity through targeted action
3Object-generated harmful factors
If Notch signaling pathway is inhibited to decrease mucus production, then respiratory disorder symptoms are ameliorated, but trans-differentiation from club cells to ciliated cells must be enhanced
Solution Approach 1:
The patent applies local quality control by selectively inhibiting Notch signaling in specific cell types (club cells and goblet cells) where it drives excessive mucus production, while allowing or promoting trans-differentiation in other contexts. The modified oligonucleotides target specific transcripts locally, creating different outcomes in different cell populations - reducing mucus in goblet cells while promoting ciliated cell differentiation from club cells
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
This approach effectively treats, prevents, or ameliorates respiratory disorders by decreasing mucus production and increasing lung function, providing therapeutic benefits for conditions like asthma, COPD, IPF, and CF by specifically targeting and modulating the Notch signaling pathway.
Implementation Method 1
a compound comprising or consisting of a modified oligonucleotide complementary to a transcript encoding a member of the Notch signaling pathway
Data Source
AI summary
Provided herein are methods, compounds, and compositions for modulating expression of at least one member of the Notch signaling pathway in a cell or individual. Such methods, compounds, and compositions are useful to treat, prevent, delay, or ameliorate a respiratory disorder associated with excessive mucus production in an individual.