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

VSEngineering 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

Engineering Contradiction:
Improvedelivery reliabilityVSAvoidtissue access capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

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

Inventive Principle:
Principle #5Merging (Combining)

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

Inventive Principle:
Principle #6Universality (Multi-functionality)

2Ease of operation

If single-stranded oligonucleotide therapeutics are used, then delivery and biodistribution are improved, but duplex activity may be compromised

Engineering Contradiction:
Improvedelivery efficiencyVSAvoidduplex activity
Core Design Contradiction:
Ease of operationVSReliability

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

Inventive Principle:
Principle #1Segmentation

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

Inventive Principle:
Principle #3Local quality

Data Source

PatentUS20250297258A1Oligonucleotide-based delivery vehicle for oligonucleotides agents and methods of use thereof
Publication Date: 2025.09.25 SINO US INST OF RNA TECH
  • US20250297258A1 patent drawing
  • US20250297258A1 patent drawing
  • US20250297258A1 patent drawing

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.