Nucleoside Derivative for RNA Drug Delivery
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Solution Overview
Problem
Current RNA drugs, such as siRNA, face challenges in cell membrane permeability and ribonuclease resistance, limiting their effectiveness in targeting specific tissues and maintaining stability during delivery.
Innovation Solution
A nucleoside derivative with a basic substituent at the 4′ position of ribose or a halogen atom at the 2′ hydroxyl group is introduced to enhance cell membrane permeability and ribonuclease resistance, allowing for improved delivery of RNA pharmaceuticals without the need for traditional delivery carriers like lipid nanoparticles.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If siRNA is used for gene suppression, then target selectivity is improved, but cell membrane permeability deteriorates
Solution Approach 1:
The patent modifies the chemical structure of siRNA by introducing a basic substituent at the 4' position of ribose, changing the physical-chemical parameters of the molecule to improve cell membrane permeability while preserving target selectivity
Solution Approach 2:
The patent creates a composite structure by combining siRNA with modified nucleoside components that have enhanced membrane permeability properties, resulting in a hybrid molecule that exhibits both target selectivity and improved cellular uptake
2Measurement precision
If siRNA is used for gene suppression, then target selectivity is improved, but ribonuclease resistance deteriorates
Solution Approach 1:
The patent changes the chemical parameters of siRNA by introducing a basic substituent at the 4' position of ribose, which alters the molecular properties to confer resistance against ribonuclease degradation while maintaining target selectivity
3Object-affected harmful factors
If delivery carriers like lipid nanoparticles are used, then cell membrane permeability is improved, but device complexity increases
Solution Approach 1:
The patent extracts and eliminates the need for complex delivery carriers like lipid nanoparticles by incorporating cell membrane permeability enhancement directly into the siRNA molecule structure itself, simplifying the overall delivery system
Solution Approach 2:
The modified siRNA molecule becomes self-sufficient by inherently possessing improved cell membrane permeability and ribonuclease resistance through its modified nucleoside structure, eliminating the need for external delivery carriers
Data Source
AI summary
A nucleoside derivative represented below, or a salt thereof.(In (1), R1 represents a hydrogen atom, a hydroxyl group or a protected group, and in (2), X represent a halogen atom. In (1) and (2), R2 and R4 each represent a hydrogen atom, a hydroxyl protecting, phosphate, or protected phosphate group, or —P(═O)nR5R6 (n is 0 or 1, R5 and R6 each representing a hydrogen atom, hydroxyl, protected hydroxyl, mercapto, protected mercapto, lower alkoxy, cyano lower alkoxy, amino or substituted amino group, when n is 1, R5 and R6 are not both hydrogen atoms), R3 represents NHR7 (R7 represents a hydrogen atom, alkyl, alkenyl or protecting group for an amino group), an azide, amidino or guanidino group, each having a linking group (when R7 is hydrogen atom, the linking group is an alkylene group), and B represents any of a purine-9-yl, 2-oxo-pyrimidin-1-yl, substituted purine-9-yl or substituted 2-oxo-pyrimidin-1-yl group).