Single-Stranded Nucleic Acid with Alicyclic Linker
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Solution Overview
Problem
Current RNA interference techniques face challenges in manufacturing efficiency and stability, particularly with siRNA requiring separate strand synthesis and hybridization, and circular RNA synthesis difficulties, along with limited options for modifying RNA molecules to impart functions or labels while maintaining gene expression inhibition.
Innovation Solution
A single-stranded nucleic acid molecule with a nitrogen-containing alicyclic skeleton, comprising an expression inhibitory sequence, a linker region with a pyrrolidine or piperidine structure, and a complementary region, which can inhibit gene expression without the need for hybridization and allows for modifications beyond conventional nucleotide alterations.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If siRNA is used to inhibit gene expression, then gene expression inhibition is achieved, but manufacturing efficiency is low due to separate strand synthesis and hybridization requirements
Solution Approach 1:
The patent combines the sense strand and antisense strand into a single-stranded nucleic acid molecule containing both complementary sequences. This merging eliminates the need for separate synthesis and hybridization steps, directly resolving the manufacturing efficiency problem while reducing process complexity from multiple steps to a single synthesis process.
Solution Approach 2:
The single-stranded nucleic acid is designed with segmented functional regions: a 5' region, a linker region with non-nucleotide structure, and a 3' region. This segmentation allows the molecule to contain both sense and antisense sequences in a controlled architecture that self-anneals to form the required double-stranded structure, simplifying manufacturing while maintaining functionality.
2Reliability
If siRNA is administered to cells, then gene expression inhibition is achieved, but handling becomes laborious due to requirements to prevent dissociation to single-stranded RNAs
Solution Approach 1:
The single-stranded nucleic acid is pre-designed with complementary sequences and a linker region that enables self-annealing to form a stable double-stranded structure. This preliminary structural arrangement ensures that the molecule remains stable during handling and administration without requiring external protection measures, directly improving ease of operation while maintaining reliability.
3Adaptability or versatility
If circular RNA is used to inhibit gene expression, then alternative RNA structure is achieved, but synthesis becomes difficult
Solution Approach 1:
Instead of using circular RNA which requires difficult cyclization synthesis, the patent inverts the approach by using a linear single-stranded nucleic acid that self-anneals to form an intramolecular double helix. This inversion maintains the functional advantages of double-stranded RNA while using a much simpler linear synthesis approach, directly resolving the synthesis difficulty problem.
4Adaptability or versatility
If conventional nucleotide modification is used to impart functions or labels, then RNA molecule function is enhanced, but modification options are limited
Solution Approach 1:
The patent introduces a linker region containing non-nucleotide structures (such as pyrrolidine or piperidine skeletons) as an intermediary between the 5' and 3' regions. This intermediary provides a versatile platform for attaching various functional groups, labels, or therapeutic moieties without requiring modification of the nucleotide sequences themselves, directly expanding modification versatility while maintaining structural simplicity.
Data Source
AI summary
Provided is a novel nucleic acid molecule that can be produced easily and efficiently and can inhibit the expression of a gene. The nucleic acid molecule is a single-stranded nucleic acid molecule including an expression inhibitory sequence that inhibits expression of a target gene. The single-stranded nucleic acid molecule includes: a region (X); a linker region (Lx); and a region (Xc). The linker region (Lx) is linked between the regions (Xc) and (Xc). The region (Xc) is complementary to the region (X). At least one of the regions (X) and (Xc) includes the expression inhibitory sequence. The linker region (Lx) has a non-nucleotide structure including at least one of a pyrrolidine skeleton and a piperidine skeleton. According to this single-stranded nucleic acid molecule, it is possible to inhibit the expression of the target gene.