Engineered Nucleic Acids Targeting lncRNA for Viral Inhibition

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Solution Overview

Problem

Current antiviral therapies for respiratory viruses such as influenza and coronaviruses are limited, with most vaccines and effective drugs not yet available, and existing research has focused primarily on host proteins rather than noncoding RNAs involved in viral pathogenesis.

Innovation Solution

Engineered nucleic acids encoding inhibitory oligonucleotides that target long non-coding RNAs (lncRNAs) involved in respiratory virus pathogenesis, specifically DGCR5, to activate the interferon pathway and inhibit viral infection and propagation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If antiviral therapies are developed for respiratory viruses, then viral pathogenesis is inhibited, but limited therapeutic options and lack of vaccines/drugs remain

Engineering Contradiction:
Improvetherapeutic effectivenessVSAvoidtherapeutic options
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent develops a universal therapeutic platform targeting host lncRNAs that can be applied across multiple respiratory viruses (influenza, coronaviruses, RSV, adenoviruses) without needing virus-specific drugs, thereby providing both reliable antiviral activity and broad adaptability through a single platform approach

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

2Loss of information

If research focuses on host proteins translated from coding regions, then protein function is understood, but the majority of the genome transcribed as noncoding RNAs remains unexplored

Engineering Contradiction:
Improvegenomic informationVSAvoidlncRNA identification
Core Design Contradiction:
Loss of informationVSDifficulty of detecting and measuring

Solution Approach 1:

The patent performs preliminary identification and characterization of lncRNAs involved in respiratory virus pathogenesis before developing therapeutics, using high-throughput sequencing and functional assays to pre-screen and validate target lncRNAs, thereby reducing subsequent development difficulties and information loss

Inventive Principle:
Principle #10Preliminary action

Solution Approach 2:

The patent uses high-throughput sequencing technology as an intermediary tool to bridge the gap between unexplored noncoding RNA regions and functional understanding, enabling systematic identification and characterization of lncRNAs that would otherwise be difficult to detect and measure

Inventive Principle:
Principle #24Intermediary (Mediator)

3Reliability

If lncRNAs are knocked down to activate interferon pathway, then type I and II interferons are up-regulated to inhibit viral infection, but the mechanism of viral pathogenesis remains complex

Engineering Contradiction:
Improveviral infection inhibitionVSAvoidpathogenesis mechanism
Core Design Contradiction:
ReliabilityVSDevice complexity

Solution Approach 1:

The patent extracts and targets specific host lncRNA molecules (such as DGCR5) that play key roles in viral pathogenesis, separating these critical regulatory elements from the complex overall pathogenesis mechanism, thereby providing reliable therapeutic intervention points while simplifying the approach to managing complexity

Inventive Principle:
Principle #2Taking out (Extraction)

Data Source

PatentUS20240093190A1Engineered nucleic acids targeting long noncoding RNA involved in pathogenic infection
Publication Date: 2024.03.21 PRESIDENT & FELLOWS OF HARVARD COLLEGE
  • US20240093190A1 patent drawing
  • US20240093190A1 patent drawing
  • US20240093190A1 patent drawing

AI summary

The present disclosure provides compositions and methods for inhibiting viral pathogenesis by targeting long noncoding ribonucleic acids.