Nucleic Acid Dimer with Circular Antisense Strand
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Solution Overview
Problem
Current nucleic acid drugs face challenges such as off-target effects, low chemical stability, and complex design or production processes in modulating gene expression effectively.
Innovation Solution
A nucleic acid molecule dimer comprising a linear first nucleic acid molecule and a circular second nucleic acid molecule, which form a duplex, with specific structural features like overhangs and modifications, designed to specifically target and modulate the expression of a target nucleic acid molecule with reduced off-target effects and enhanced stability.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional nucleic acid drugs are used to modulate gene expression, then gene expression can be controlled, but off-target effects occur and chemical stability is low
Solution Approach 1:
The invention divides the nucleic acid drug into two separate strands: a sense strand and an antisense strand. These strands are administered separately and assemble at the target site to form a duplex structure. This segmentation allows each strand to be optimized independently for stability and delivery, while the assembled duplex provides high specificity to reduce off-target effects.
Solution Approach 2:
The circular RNA component acts as an intermediary structure that protects the nucleic acid sequence from degradation while facilitating targeted delivery. The circular structure serves as a stable scaffold that maintains the integrity of the antisense sequence until it reaches the target site, where it assembles with the sense strand to form the active duplex.
2Reliability
If conventional nucleic acid drugs are used to modulate gene expression, then gene expression can be controlled, but chemical stability is low
Solution Approach 1:
The nucleic acid drug is segmented into two separate strands with different stability characteristics. The circular RNA strand provides enhanced chemical stability and resistance to nucleases, while the linear sense strand maintains flexibility for delivery. This segmentation allows the stable circular strand to protect the overall complex from degradation in the bloodstream.
Solution Approach 2:
The invention creates a composite nucleic acid structure combining circular RNA and linear sense RNA strands. This composite structure leverages the superior chemical stability and nuclease resistance of circular RNA while incorporating the functional versatility of linear RNA, resulting in a drug with enhanced overall stability and performance.
3Object-affected harmful factors
If complex nucleic acid structures are designed to reduce off-target effects, then specificity improves, but design and production complexity increases
Solution Approach 1:
The complex nucleic acid structure is divided into two simpler strands that can be designed and synthesized independently using standard protocols. The circular RNA strand and linear sense strand are each optimized separately, then assembled at the target site. This segmentation simplifies the design process while maintaining the high specificity of the duplex structure.
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 nucleic acid molecule dimer effectively modulates target nucleic acid expression with reduced off-target effects, stability in blood, resistance to nuclease, and ease of design and production, while avoiding sequence-non-specific cell responses and activation of pathways like PKR and TLR3.
Implementation Method 1
a first nucleic acid molecule having complementarity to at least a portion of a target nucleic acid molecule; and a second nucleic acid molecule having complementarity to the first nucleic acid molecule, wherein the first nucleic acid molecule and the second nucleic acid molecule at least partially form a duplex
Data Source
AI summary
The present invention provides a nucleic acid molecule dimer that includes a first nucleic acid molecule having complementarity with at least part of a target nucleic acid molecule, and a second nucleic acid molecule having complementarity with the first nucleic acid molecule, wherein the first nucleic acid molecule has a linear form, the second nucleic acid molecule has a cyclic form, and the first and second nucleic acid molecules at least partially form a double strand.