Synthetic-Backbone Oligonucleotides for Targeted Cellular Delivery
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Solution Overview
Problem
Existing delivery methods for therapeutic, prophylactic, or diagnostic compounds often result in unintended consequences due to off-target effects, necessitating improved localization and efficiency of compound delivery to specific cellular targets.
Innovation Solution
Development of modified oligonucleotides with specific backbones and chemical modifications, such as those represented by Formulas (I) to (XVIII), which can be administered with targeting ligands to enhance localization and modulate target nucleic acids or proteins, thereby treating diseases and disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional delivery methods are used for therapeutic compounds, then the compounds can be administered to subjects, but off-target effects occur and localization to specific locations is poor
Solution Approach 1:
The patent employs targeting ligands as intermediary molecules that mediate between the therapeutic oligonucleotide and the target cell. These ligands bind to specific receptors on the cell surface, facilitating selective delivery of the oligonucleotide to the desired location while preventing off-target effects through receptor specificity.
Solution Approach 2:
The patent applies local quality by modifying the oligonucleotide with location-specific targeting ligands that confer different localization properties to different oligonucleotide molecules. This allows specific regions of the body (such as the brain) to be targeted preferentially, improving delivery specificity to the intended target location.
2Productivity
If oligonucleotides are delivered to modulate target nucleic acids, then gene expression can be changed, but the delivery efficiency to specific cellular targets is insufficient
Solution Approach 1:
Targeting ligands serve as intermediaries that enhance delivery efficiency by mediating the interaction between the oligonucleotide and target cells. The ligands bind to cell surface receptors, facilitating efficient uptake of the oligonucleotide into the target cell while maintaining high target localization specificity.
Solution Approach 2:
The patent modifies the chemical parameters of the oligonucleotide by incorporating different targeting ligands that change the delivery characteristics. These parameter changes in the oligonucleotide structure enable optimized delivery efficiency to specific cellular targets while maintaining localization accuracy.
3Reliability
If chemical modifications are made to oligonucleotides to improve delivery, then therapeutic outcomes can be enhanced, but the synthesis complexity increases
Solution Approach 1:
The patent applies segmentation by dividing the oligonucleotide modification process into separate steps: first synthesizing the core oligonucleotide sequence, then separately incorporating targeting ligands at specific positions. This segmentation allows for modular assembly, reducing overall synthesis complexity while maintaining therapeutic efficacy through precise chemical modifications.
Solution Approach 2:
The patent creates composite oligonucleotide structures by combining the core nucleic acid sequence with chemically modified regions and attached targeting ligands. These composite materials integrate multiple functional elements (therapeutic sequence + delivery moieties) into a single molecule, enhancing therapeutic outcomes while managing synthesis complexity through standardized conjugation methods.
Data Source
AI summary
Provided herein are oligonucleotide-containing compounds, methods of delivering the compounds, and methods of treating diseases, disorders, and symptoms (e.g., central nervous system diseases, disorders, and symptoms) in a subject using the compounds.