Single-Stranded Oligonucleotide with Non-Nucleotide Linker
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Solution Overview
Problem
Current antisense oligonucleotides face challenges with degradation in the body and low uptake efficiency into target cells, and the production of double-stranded oligonucleotides is complex, requiring separate synthesis of antisense and complementary strands and maintaining their hybridization.
Innovation Solution
A single-stranded oligonucleotide is developed by coupling an antisense oligonucleotide with its complementary RNA strand using a linker containing a non-nucleotide structure, allowing partial hybridization within the molecule, which enhances antisense effects similar to double-stranded oligonucleotides without the need for complex hybridization steps.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If double-stranded oligonucleotides are used to enhance antisense effects, then target gene suppression efficiency is improved, but production complexity increases due to separate synthesis and hybridization steps
Solution Approach 1:
The patent merges the antisense strand and complementary strand into a single-stranded oligonucleotide structure where the complementary strand is covalently linked to the antisense strand. This eliminates the need for separate synthesis and hybridization steps while maintaining the functional capabilities of double-stranded structures for target gene suppression.
Solution Approach 2:
The single-stranded oligonucleotide is designed with distinct functional segments: an antisense sequence portion for target RNA binding and a complementary sequence portion that forms intramolecular hybridization. This segmentation allows each portion to perform its specific function while being synthesized as a single molecule.
2Ease of manufacture
If conventional antisense oligonucleotides are used, then synthesis is simple, but uptake efficiency into target cells is low
Solution Approach 1:
The patent combines the antisense sequence with a complementary sequence in a single-stranded structure, creating an oligonucleotide that can be synthesized as a single molecule while maintaining enhanced cellular uptake efficiency through the integrated structure that facilitates cell penetration and target engagement.
3Productivity
If double-stranded oligonucleotides are used to improve antisense effects, then target suppression is enhanced, but the process requires maintaining hybridization which adds operational complexity
Solution Approach 1:
The single-stranded oligonucleotide is designed with an antisense sequence portion and a complementary sequence portion that can form intramolecular hybridization. This segmentation allows the molecule to maintain structural stability for enhanced target suppression while simplifying handling by eliminating the need to maintain separate strands and their hybridization.
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 single-stranded oligonucleotide achieves high-efficiency target gene suppression with simplified production, demonstrating antisense effects comparable to double-stranded oligonucleotides while avoiding the complexity of forming a double strand.
Implementation Method 1
coupling an antisense oligonucleotide with its complementary RNA strand using a linker containing a non-nucleotide structure, allowing partial hybridization within the molecule
Data Source
AI summary
The invention provides a single-stranded oligonucleotide represented by the formula (I), wherein X and Y hybridize by a first nucleotide sequence portion and a second nucleotide sequence portion. X is composed of 7 to 100 nucleotides, contains at least one modified-nucleotide, and has a first nucleotide sequence capable of hybridizing with a second oligonucleotide. Y is composed of 4 to 100 nucleotides, enables hybridization with the above-mentioned first oligonucleotide, and has a second nucleotide sequence containing at least one ribonucleotide. At least one of the nucleotide sequences X, Xz and Y has an antisense sequence capable of hybridizing with a target RNA. At least one of L, Lx and Ly is a linking group that contains a non-nucleotide structure.