Oligonucleotide-Based Delivery Vehicle for Tissue Access
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Solution Overview
Problem
Existing oligonucleotide delivery technologies face challenges in providing access to target tissues, organs, or cell types, limiting the therapeutic potential of oligonucleotide-based therapies.
Innovation Solution
A novel oligonucleotide agent comprising a double-stranded RNA (dsRNA) covalently tethered to a non-targeting accessory oligonucleotide (ACO) forms an oligonucleotide-based delivery vehicle (ODV) with self-delivering properties, enhancing biodistribution and activity across various organs and tissues.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional oligonucleotide delivery technologies are used, then delivery to target tissues is limited, but the therapeutic potential of oligonucleotide-based therapies is restricted
Solution Approach 1:
The patent combines a double-stranded RNA (dsRNA) with a single-stranded accessory oligonucleotide (ACO) into a single conjugated molecule. The dsRNA provides the therapeutic function while the ACO provides delivery capabilities, creating an integrated system that achieves both reliable delivery and broad tissue access without requiring separate delivery vehicles
Solution Approach 2:
The accessory oligonucleotide component is designed to be non-targeting and non-complementary to any specific sequence, giving it universal delivery properties. This allows the same ACO structure to deliver the dsRNA to multiple different tissue types and cell types systemically, enhancing adaptability while maintaining delivery reliability
2Ease of operation
If single-stranded oligonucleotide therapeutics are used, then delivery and biodistribution are improved, but duplex activity may be compromised
Solution Approach 1:
The oligonucleotide agent is segmented into two distinct functional components: a dsRNA segment that maintains duplex structure and therapeutic activity, and a single-stranded ACO segment that provides delivery advantages. The covalent connection between segments allows each to perform its specialized function without interfering with the other's structural integrity or activity
Solution Approach 2:
Different regions of the oligonucleotide agent have different structural and functional properties. The dsRNA region maintains its double-stranded structure for therapeutic activity while the ACO region adopts a single-stranded configuration optimized for delivery. This local differentiation allows simultaneous optimization of both delivery efficiency and duplex activity
Data Source
AI summary
Provided are nucleic acids, specifically as it relates to an oligonucleotide agent comprising a double-stranded RNA (dsRNA, duplex) and a non-targeting accessory oligonucleotide (ACO) that is covalently tethered to the dsRNA and pharmaceutical use thereof.


