Hydrolysable Oligonucleotide Linker for Multi-mRNA Delivery
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Solution Overview
Problem
Existing oligonucleotide delivery technologies lack novel hydrolysable linkers capable of simultaneously delivering multiple oligonucleotides, leading to issues with gene activity and stability.
Innovation Solution
A hydrolysable linker structure is developed, allowing for the covalent attachment of two or more oligonucleotides, which can bind to the same or different positions of target mRNA, and is designed to release oligonucleotides through hydrolysis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If existing oligonucleotide delivery technologies are used, then single oligonucleotide delivery is achieved, but multiple oligonucleotide delivery capability is lacking
Solution Approach 1:
The linker is divided into distinct functional segments: a first portion that binds to a first oligonucleotide, a second portion that binds to a second oligonucleotide, and a connecting portion that joins these portions together. This segmentation allows each portion to be optimized for specific binding characteristics while enabling the overall linker to carry multiple oligonucleotides simultaneously.
Solution Approach 2:
The linker is designed as a multi-functional molecule that can simultaneously bind to different oligonucleotides through its multiple binding portions. Each binding portion can recognize and attach to specific oligonucleotide sequences, allowing the single linker structure to perform multiple delivery functions at once.
2Ease of operation
If hydrolysable linker is designed to release oligonucleotides, then delivery control is improved, but stability during circulation may be compromised
Solution Approach 1:
The linker incorporates hydrolyzable bonds with specific kinetic parameters that allow stable circulation during the half-life of the oligonucleotide, yet enable controlled release afterward. The hydrolysis rate can be adjusted by selecting appropriate bond types and chemical environments, creating a temporal separation between stability and release phases.
Solution Approach 2:
The hydrolysable bond acts as an intermediary mechanism between the stable linker-oligonucleotide complex during circulation and the released oligonucleotide after delivery. This intermediate bond maintains structural integrity during circulation but facilitates controlled dissociation under physiological conditions after the oligonucleotide has performed its function.
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 linker enhances the delivery and stability of multiple oligonucleotides, improving gene modulation efficacy and stability, enabling targeted gene silencing with reduced side effects.
Implementation Method 1
the linker is hydrolysable. The linker may be linked to oligonucleotides through positions shown by wavy lines, and may be hydrolyzed to release the oligonucleotides linked thereto
Data Source
AI summary
The present disclosure relates to the technical field of biological delivery, and discloses a linker with a specific structure, a compound including the linker, a method of preparing the compound, use of the linker, and a method of delivering oligonucleotides through the linker. The linker of the present disclosure may be linked to the oligonucleotides, and may be hydrolyzed to release the oligonucleotides linked thereto, and the oligonucleotides bind to the same or different positions of the same target mRNA, or the oligonucleotides bind to two or more target mRNAs.