Cell Membrane-Permeable Nucleic Acid for Reagent-Free siRNA Delivery
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Solution Overview
Problem
Nucleic acids face challenges with low stability and poor cell membrane permeability, necessitating additional carriers for effective delivery into cells, and existing modifications with polyfluoro structures do not adequately address these issues.
Innovation Solution
A nucleic acid is developed by linking a cell membrane-permeable group, represented by specific alkyl or perfluoroalkyl structures, to the nucleic acid, enhancing its permeability without the need for separate transfection reagents.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If nucleic acid drugs are administered to improve stability and specificity, then drug efficacy is improved, but cell membrane permeability deteriorates making delivery difficult
Solution Approach 1:
The patent applies local quality by introducing polyfluoro structures at specific positions within the nucleic acid molecule rather than modifying the entire structure. The polyfluoro groups are strategically placed on side chains or terminal positions to locally enhance membrane permeability while preserving the overall stability and functionality of the nucleic acid drug.
Solution Approach 2:
The patent creates composite nucleic acid structures by combining natural or artificial nucleic acid backbones with polyfluoro-containing side chains or terminal groups. This composite approach integrates the stability of nucleic acid drugs with the membrane-permeable properties of polyfluoro structures, achieving both improved stability and enhanced cell membrane permeability simultaneously.
2Ease of operation
If polyfluoro structures are introduced to improve cell membrane permeability, then permeability is improved, but synthesis complexity increases
Solution Approach 1:
The patent employs segmentation by dividing the nucleic acid molecule into distinct functional modules: a stable nucleic acid backbone and separate polyfluoro-containing side chain or terminal groups. This modular design allows the polyfluoro structures to be synthesized and attached independently, simplifying the overall synthesis process compared to attempting to create entirely new complex molecules.
Solution Approach 2:
The patent uses linkers or connecting groups as intermediaries between the nucleic acid backbone and the polyfluoro structures. These intermediary elements facilitate the attachment of polyfluoro groups while maintaining synthetic accessibility and allowing for standardized synthesis protocols to be used for both the nucleic acid and polyfluoro components separately.
3Reliability
If siRNA is used for targeted delivery, then specificity is improved, but molecular weight increases reducing permeability
Solution Approach 1:
The patent applies local quality by attaching polyfluoro structures to specific positions on the siRNA molecule, such as terminal nucleotides or side chain positions, rather than increasing the overall molecular size. This localized modification enhances membrane permeability without significantly increasing molecular weight or compromising the target-specific binding capability of the siRNA sequence.
Data Source
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AI summary
The present invention provides a nucleic acid for transfection having excellent cell membrane permeability, and a method for producing the nucleic acid. The present invention relates to a nucleic acid for transfection, in which a nucleic acid targeted for introduction into a cell and a cell membrane-permeable group are linked together, and the cell membrane-permeable group has a structure represented by one of general formulas (A1) to (A4) (wherein in the formulas: R0 represents an alkyl group of 1 to 30 carbon atoms which may have an ether-bonded oxygen atom between carbon atoms and may be substituted with one or more fluorine atoms; n11, n12, n13 and n14 each independently represent an integer of 1 or greater; B represents a nucleic acid base; RFE represents a perfluoroalkyl group of 1 to 10 carbon atoms which may have an ether-bonded oxygen atom between carbon atoms; na represents an integer of 1 to 10; and the black dots indicate bonding sites).