Toehold Riboregulators for Specific Viral and TF RNA Detection

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Solution Overview

Problem

Existing technologies lack effective methods for detecting specific viral nucleic acids or human transcription factors associated with viral infections or cancers using engineered ribonucleic acid (RNA) molecules.

Innovation Solution

Development of toehold riboregulators with specific nucleic acid sequences (SEQ ID NOs: 43841, 9602, 62866, 19367, 164989, 111698, and 236638) that can hybridize with viral nucleic acids or human transcription factor mRNAs, allowing detection and measurement of their presence or level, and potentially triggering reporter protein expression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Measurement precision

If conventional RNA-based diagnostic tools are used, then detection capability is provided, but specificity and sensitivity are insufficient

Engineering Contradiction:
Improvedetection specificity and sensitivityVSAvoiddiagnostic accuracy
Core Design Contradiction:
Measurement precisionVSReliability

Solution Approach 1:

The toehold riboregulator employs a specialized local structure (the toehold region) with distinct properties that enables selective binding. The toehold sequence is designed to be complementary to the target viral or transcription factor nucleic acid, creating a localized high-affinity binding site that enhances both specificity and sensitivity of detection

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The riboregulator is divided into functional segments including the toehold region, stem-loop structure, and reporter domain. This segmentation allows each region to perform its specific function: the toehold for selective recognition, the stem-loop for structural stability and conformational change, and the reporter for signal generation

Inventive Principle:
Principle #1Segmentation

2Measurement precision

If existing diagnostic methods are used, then general detection is possible, but accurate identification of specific viral infections and cancer conditions is limited

Engineering Contradiction:
Improvedetection accuracyVSAvoiddetection system complexity
Core Design Contradiction:
Measurement precisionVSDevice complexity

Solution Approach 1:

The toehold riboregulator acts as an intermediary molecule that bridges the target nucleic acid (viral genome or transcription factor mRNA) and the reporter system. It specifically recognizes and binds to the target sequence, then triggers a conformational change that activates reporter expression, thereby mediating the detection process with high precision

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The riboregulator system is self-amplifying through the trigger-induced conformational change that activates reporter protein expression. The binding of the target nucleic acid to the toehold region automatically triggers the structural rearrangement and subsequent reporter activation without requiring external intervention, enabling sensitive and accurate detection

Inventive Principle:
Principle #25Self-service

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

Enables accurate detection and measurement of viral infections or cancer-related transcription factors, facilitating targeted treatment with anti-viral or anti-cancer agents.

Implementation Method 1

these riboregulators hybridize with these targets, enabling detection and measurement

Methodology Applied
Scientific EffectNucleic acid hybridization:

Data Source

PatentUS12624385B2Riboregulators and methods of use thereof
Publication Date: 2026.05.12 MASSACHUSETTS INST OF TECH
  • US12624385B2 patent drawing
  • US12624385B2 patent drawing
  • US12624385B2 patent drawing

AI summary

This disclosure provides riboregulators specific for particular viruses or for particular human transcription factors. The viral-specific riboregulators may be used to detect the presence of the particular virus, and this may enable diagnosis of an infection. The transcription factor specific riboregulators may be used to detect the presence and/or measure the level of the particular transcription factor, and this may enable diagnosis or prognosis of a particular condition such as cancer.