Open Circular Nucleic Acid Monomer for Enhanced siRNA Stability
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Solution Overview
Problem
Current modified nucleic acids are insufficient in biological stability and suppressive activity against target gene expression, limiting their effectiveness in therapeutic and diagnostic applications.
Innovation Solution
An open circular nucleic acid monomer compound with a carbon-carbon bond cleaved at the 2'- and 3'-positions and a substituted hydroxymethyl group at the 4'-position is used to enhance the stability and suppressive activity of oligonucleic acid analogs, such as siRNA, for improved gene expression inhibition and diagnostic tools.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If naturally occurring DNA or RNA oligomers are used, then they can perform basic functions in antisense method and RNAi method, but they are very unstable biologically due to rapid hydrolysis by nucleases in blood
Solution Approach 1:
The patent modifies the chemical structure of nucleic acid monomers by changing parameters such as the sugar moiety configuration (cleaved at 2'- and 3'-positions to form open circular structure with substituted hydroxymethyl group at 4'-position), which fundamentally alters the molecule's resistance to nuclease hydrolysis while preserving its biological function
Solution Approach 2:
The invention creates composite modified nucleic acid structures by combining the open circular monomer unit with nucleobases and phosphate groups, forming a hybrid structure that integrates the stability benefits of the modified sugar moiety with the functional properties of natural nucleic acid components
2Stability of the object's composition
If modified nucleic acids are used to improve stability, then biological stability is enhanced, but suppressive activity against target gene expression is insufficient
Solution Approach 1:
The patent applies local quality modification by specifically altering the sugar moiety structure at the 2'- and 3'-positions while maintaining the natural nucleobase and phosphate backbone, thereby locally enhancing stability without compromising the overall suppressive activity against target gene expression
Solution Approach 2:
The invention optimizes suppressive activity by adjusting parameters of the modified monomer structure, including the substitution pattern at the 4'-position hydroxymethyl group, to achieve optimal balance between stability and gene suppressive activity
Data Source
AI summary
Provided is an oligonucleic acid analog which contains, as at least one structural unit thereof, a modified nucleic acid monomer compound which is a ring-open nucleoside having a cleaved carbon-carbon bond between the 2' and 3' positions and a substituent hydroxymethyl group at the 4' position. When used as siRNA, the oligonucleic acid analog exhibits superior biological stability and target gene expression inhibiting activity. The oligonucleic acid analog can be used in antisense methods, ribozyme methods, and decoy methods, etc., can be used as a nucleic acid aptamer, and can also be used as a nucleic acid probe or molecular beacon, etc., or in genetic diagnostics, etc.