Lipid-Conjugated Nucleic Acid Complex for Ischemic Site Targeting
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Solution Overview
Problem
Current nucleic acid medicines, such as antisense nucleic acids and siRNA, are insufficient in modulating gene expression specifically at ischemic sites, which are critical for treating vascular disorders like ischemic stroke and heart disease.
Innovation Solution
A nucleic acid complex is developed by annealing an antisense oligonucleotide with a lipid-conjugated complementary strand, enhancing delivery efficiency to ischemic sites for targeted modulation of transcriptional products.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional antisense nucleic acids or siRNA are administered, then gene expression modulation is achieved, but delivery efficiency to ischemic sites is insufficient
Solution Approach 1:
The patent employs an ischemic site-specific binding molecule (such as a peptide or antibody) as an intermediary carrier that selectively binds to receptors or markers overexpressed at ischemic sites. This intermediary facilitates targeted delivery of the antisense nucleic acid or siRNA to the ischemic region, resolving the contradiction between achieving gene modulation and ensuring sufficient delivery efficiency to the target site.
Solution Approach 2:
The invention creates a localized therapeutic effect by conjugating the antisense nucleic acid or siRNA with a binding molecule that specifically targets ischemic tissue. This ensures that the gene expression modulation occurs preferentially at the ischemic site rather than systemically, improving both delivery efficiency to the target and the overall effectiveness of the treatment.
2Measurement precision
If systemic administration of nucleic acid medicine is performed, then gene expression can be modulated throughout the body, but specificity to ischemic sites is reduced
Solution Approach 1:
The patent implements local quality by designing a conjugate where the antisense nucleic acid or siRNA is attached to an ischemic site-specific binding molecule. This ensures that while the drug can be administered systemically, it accumulates and exerts its effect preferentially at ischemic sites where the target receptors or markers are present, thereby achieving both systemic delivery and localized specificity.
Solution Approach 2:
The binding molecule acts as an intermediary that mediates between systemic circulation and ischemic target sites. It enables the nucleic acid therapeutic to navigate the bloodstream and selectively bind to ischemic tissue, achieving high targeting specificity without sacrificing the ability to administer the therapy systemically.
3Reliability
If higher doses of nucleic acid medicine are administered to improve delivery efficiency, then gene modulation effectiveness increases, but off-target effects and toxicity increase
Solution Approach 1:
The invention achieves high delivery efficiency at low doses by concentrating the therapeutic agent specifically at ischemic sites through the binding molecule. This localized delivery ensures that effective gene modulation occurs at the target site without requiring high systemic doses, thereby minimizing off-target effects and toxicity while maintaining reliable therapeutic effectiveness.
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 complex effectively delivers therapeutic oligonucleotides to ischemic sites, selectively modulating gene expression and improving treatment outcomes for ischemic diseases by increasing delivery efficiency and specificity.
Implementation Method 1
a nucleic acid complex formed by annealing together a first nucleic acid strand comprising an antisense oligonucleotide region with respect to a target transcriptional product, and a lipid-conjugated second nucleic acid strand comprising a complementary region that is complementary to at least part of the first nucleic acid strand
Data Source
Figure 1A~1B
Figure 2A~2C
Figure 3A~3B
AI summary
In an embodiment, the present invention provides an antisense nucleic acid medicine that can modulate expression of a target transcriptional product in an ischemic site of a subject. In an embodiment, the present invention provides a composition for modulating expression of a target transcriptional product in an ischemic site of a subject, comprising a nucleic acid complex formed by annealing together a first nucleic acid strand comprising an antisense oligonucleotide region with respect to the target transcriptional product, and a lipid-conjugated second nucleic acid strand comprising a complementary region that is complementary to at least part of the first nucleic acid strand.