Abasic Nucleoside Oligonucleotides for Sustained Gene Silencing
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Solution Overview
Problem
Current oligonucleotide/oligonucleoside compounds for gene silencing have limitations in effectively targeting and inhibiting specific gene expression in therapeutic applications, particularly in diseases such as cancer and metabolic disorders, where precise and sustained suppression of target genes is needed.
Innovation Solution
Development of nucleic acid compounds with duplex regions comprising complementary strands and abasic nucleosides in terminal regions, connected through reversed internucleoside linkages, which form specific conjugates to inhibit target gene expression by forming stable complexes with RNA transcripts.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional oligonucleotide compounds are used for gene silencing, then gene expression can be inhibited, but the suppression is not sufficiently sustained or effective in therapeutic applications
Solution Approach 1:
The patent modifies the chemical structure of oligonucleotide compounds by incorporating abasic nucleosides and reversed internucleoside linkages, changing the physical and chemical parameters of the molecule to achieve both effective and sustained gene silencing. This structural parameter change allows the compound to maintain stability while achieving prolonged therapeutic effect.
Solution Approach 2:
The invention creates composite oligonucleotide structures combining abasic nucleosides with reversed linkages and conjugating them to targeting ligands. This composite approach integrates multiple functional elements (gene silencing capability, stability, and targeted delivery) into a single therapeutic agent that achieves both effectiveness and sustained action.
2Manufacturing precision
If oligonucleotide compounds are designed for specific gene targeting, then precision in inhibiting target gene expression is improved, but the complexity of the compound structure increases
Solution Approach 1:
The oligonucleotide compound is segmented into distinct functional modules: abasic nucleosides for structural stability, reversed internucleoside linkages for enhanced resistance to degradation, and conjugated ligands for targeted delivery. This segmentation allows each component to perform its specific function while simplifying the overall design and manufacturing process.
Solution Approach 2:
The abasic nucleoside core structure serves multiple functions simultaneously: it provides structural stability, resists enzymatic degradation, and offers a platform for conjugating various targeting ligands. This multi-functionality reduces the need for separate modifications and simplifies the overall molecular design.
Data Source
AI summary
The present invention relates to nucleic acid molecules for use in the treatment or prevention of disease.