GLP-1 Ligand Oligonucleotide Conjugates for Selective Cell Targeting
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Solution Overview
Problem
Existing technologies lack effective methods for modulating the expression of nucleic acids in cells expressing the GLP-1 receptor, particularly for therapeutic applications such as targeting pancreatic beta-islet cells and treating cancer.
Innovation Solution
Development of modified oligonucleotides conjugated with GLP-1 receptor ligands, comprising modified internucleoside linkages, sugars, and nucleobases, which hybridize specifically to target nucleic acids in cells expressing the GLP-1 receptor, thereby modulating their expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional oligonucleotides are used, then they can hybridize to target nucleic acids, but they lack selective targeting capability for GLP-1 receptor expressing cells
Solution Approach 1:
The patent merges a GLP-1 receptor ligand moiety with an oligonucleotide through a conjugate linker to create a unified compound that combines the targeting capability of the ligand with the nucleic acid modulation capability of the oligonucleotide, enabling selective delivery to GLP-1 receptor expressing cells
Solution Approach 2:
The conjugate linker serves as an intermediary component that chemically connects the GLP-1 receptor ligand moiety to the oligonucleotide, facilitating the transfer and stabilization of the conjugated compound while enabling selective cell targeting
2Reliability
If modified oligonucleotides are developed for selective targeting, then therapeutic efficacy is improved, but manufacturing complexity increases
Solution Approach 1:
The patent introduces modifications at specific local positions within the oligonucleotide structure, including modified internucleoside linkages at particular positions, modified sugars at specific locations, and modified nucleobases at defined positions, rather than uniformly modifying the entire oligonucleotide, thereby achieving enhanced stability and targeting while maintaining manufacturing feasibility
3Reliability
If conventional nucleic acid modulation methods are used, then they can modulate gene expression, but they cannot specifically target pancreatic beta-islet cells or cancer cells expressing GLP-1 receptor
Solution Approach 1:
The patent combines the GLP-1 receptor ligand moiety with the oligonucleotide to create a conjugated compound that integrates the cell-specific targeting function of the ligand with the gene expression modulation function of the oligonucleotide, achieving selective delivery to pancreatic beta-islet cells and cancer cells that express the GLP-1 receptor
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 modified oligonucleotides demonstrate selective targeting and modulation of nucleic acid expression in GLP-1 receptor-expressing cells, providing potential therapeutic benefits including treatment of cancer.
Implementation Method 1
the compound is capable of hybridizing to the target nucleic acid, resulting in at least one antisense activity
Implementation Method 2
the GLP-1 receptor is a class 2, G protein-coupled receptor that couples to adenylate cyclase via a stimulatory G protein receptor. Circulating GLP-1 binds to the GLP-1 receptor on the beta islet cells of the pancreas
Data Source
Figure 1A~1B
Figure 2A~2C
Figure 3A~3C
AI summary
The present embodiments provide compounds and methods for targeting cells expressing GLP-1 receptor.