Shikimic Acid Multidentate Splitters for Nucleic Acid Delivery
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Solution Overview
Problem
There is a need for alternative chemical functionalities to couple cargo moieties and ligands for delivering therapeutic nucleic acids to cells, particularly for targeted delivery to liver cells.
Innovation Solution
The use of multidentate 'splitter' compounds derived from or chemically related to shikimic acid to join monosaccharide ligands and nucleic acids, providing a novel approach for coupling targeting and cargo moieties.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional coupling chemistries are used to link ligands and cargo moieties to branched core structures, then existing complexes can be prepared, but alternative chemical functionalities are needed to improve targeting and pharmacokinetic properties
Solution Approach 1:
The patent applies parameter changes by modifying the chemical functionality of the coupling agents. Specifically, it introduces multidentate splitters derived from shikimic acid, which contain multiple carboxylate groups that can form coordinate covalent bonds with metal ions. This chemical parameter change enables improved targeting efficiency and pharmacokinetic properties compared to conventional coupling chemistries.
Solution Approach 2:
The patent employs composite materials by creating complexes that integrate multiple components: multidentate shikimic acid-derived splitters, metal ions (such as gallium or indium), monosaccharide ligands (like GalNAc), and cargo moieties (such as oligonucleotides). This composite structure combines the advantages of each component to achieve superior targeting and delivery performance.
2Productivity
If multivalent complexes with multiple ligands and cargo moieties are constructed using branched core structures, then targeted delivery capability is enhanced, but chemical complexity of coupling increases
Solution Approach 1:
The patent applies segmentation by dividing the complex into distinct functional modules: a multidentate splitter core derived from shikimic acid, metal ion coordination centers, ligand attachment points, and cargo moieties. This modular segmentation allows for systematic construction of multivalent complexes while managing chemical complexity through standardized coupling interfaces.
Solution Approach 2:
The multidentate shikimic acid-derived splitters serve multiple functions simultaneously: they act as structural cores, provide metal ion coordination sites, offer multiple attachment points for ligands and cargo moieties, and enable controlled assembly of complex structures. This multi-functionality reduces the need for separate components and simplifies the overall chemical architecture.
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 described compounds exhibit improved targeting, increased activity, and enhanced pharmacokinetic properties, enabling effective delivery of nucleic acids to liver cells.
Implementation Method 1
These compounds comprise specific monosaccharides which are capable of binding to asialoglycoprotein receptors (ASGPRs)
Data Source
AI summary
Provided are multivalent saccharide-containing compounds which are bonded to nucleic acids. These compounds contain a shikimic acid-derived core and are useful for delivering nucleic acids to cells or tissues, e.g. for use in therapeutic treatments. Also provided are pharmaceutical compositions comprising the aforementioned compounds and medical uses of the same, including their use in treating or preventing conditions such as liver diseases.