Peptide Nucleic Acid Complex for Endosomal Escape
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Solution Overview
Problem
Current nucleic acid-based therapeutic agents face challenges such as low cell membrane permeability, susceptibility to nuclease degradation, and inefficient endosomal escape, limiting their effectiveness in delivering bioactive nucleic acids into cells.
Innovation Solution
A nucleic acid complex is developed where a bioactive nucleic acid is complementarily bound to a carrier peptide nucleic acid, with a material for facilitating endosomal escape, such as GLFDIIKKIAESF or histidine, to enhance intracellular delivery and gene expression regulation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If peptide nucleic acid is used as a carrier to deliver bioactive nucleic acid, then binding affinity and stability are improved, but cell permeability deteriorates due to electrical neutrality
Solution Approach 1:
The patent modifies the electrical charge parameter of the peptide nucleic acid carrier from neutral to positively charged by incorporating cationic amino acids (lysine, arginine, histidine) into the peptide backbone. This charge modification enables the carrier to interact with negatively charged cell membranes through electrostatic attraction, thereby improving cell permeability while maintaining the original high binding affinity and stability characteristics of the peptide nucleic acid structure.
2Device complexity
If conventional nucleic acid delivery methods are used, then simplicity is maintained, but endosomal escape efficiency deteriorates
Solution Approach 1:
The patent employs proton sponge (histidine-rich peptide) as an intermediary substance that accumulates protons in the endosomal compartment, causing osmotic swelling and membrane disruption. This intermediary mechanism enables efficient endosomal escape of the bioactive nucleic acid without requiring complex external delivery systems, thereby maintaining simplicity while dramatically improving endosomal escape efficiency.
3Productivity
If nucleic acid is introduced into cells, then gene expression regulation is achieved, but nuclease degradation increases susceptibility
Solution Approach 1:
The patent creates a composite protective structure by wrapping the bioactive nucleic acid in a peptide nucleic acid carrier shell. This composite configuration shields the nucleic acid from nuclease enzymes in the cellular environment, preventing degradation while allowing the inner nucleic acid to maintain its gene expression regulation function. The peptide nucleic acid outer layer acts as a protective barrier that is both stable and biocompatible.
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 complex significantly increases cell permeability and intracellular activity of bioactive nucleic acids, allowing for efficient regulation of target gene expression and improved therapeutic outcomes.
Implementation Method 1
a bioactive nucleic acid and a carrier peptide nucleic acid are complementarily bound to each other
Implementation Method 2
a material for facilitating endosomal escape of the bioactive nucleic acid and the carrier peptide nucleic acid
Data Source
Figure 1a(1)
Figure 1a(1)
Figure 1a(1)
AI summary
The present invention relates to a nucleic acid complex having a novel structure, which may introduce a bioactive nucleic acid into cells, a composition for treating or diagnosing disease comprising the same, and a method of regulating target gene expression using the same, and more particularly to a nucleic acid complex in which a bioactive nucleic acid, which comprises a material for facilitating endosomal escape, and a carrier peptide nucleic acid, are complementarily bound to each other, a composition for treating or diagnosing disease comprising the same, a composition for regulating target gene expression using the same, and a method of regulating target gene expression using the same. A nucleic acid complex of Structural Formula (1) according to the present invention, which comprises a bioactive nucleic acid and a carrier peptide nucleic acid, may increase the stability of the bioactive nucleic acid, reduce loss of the bioactive nucleic acid, such as precipitation caused by self-aggregation, increase the intracellular delivery efficiency of the bioactive nucleic acid, and easily regulate target gene expression.