Self-Assembled RNA Constructs for Direct Reprogramming

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Solution Overview

Problem

Current direct reprogramming technologies face challenges such as low conversion efficiency, instability of RNA-based methods, and risks of infection or genetic modification associated with virus- or DNA-based gene delivery, which limit their application in cell therapy.

Innovation Solution

A composition comprising self-assembled three-dimensional RNA constructs that express or inhibit transcription factors, providing stability and high efficiency for direct reprogramming without the risks of genetic modification or infection, with the constructs maintaining activity for extended periods.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If virus- or DNA-based delivery is used for direct reprogramming, then gene delivery can be achieved, but the risk of infection or permanent genetic modification increases

Engineering Contradiction:

Improvesafety of gene deliveryVSAvoidrisk of infection or genetic modification

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the harmful components (virus vectors and permanent DNA integration) from the gene delivery system, using only transient RNA molecules that do not integrate into the genome. The RNA-based approach eliminates the risk of viral infection and permanent genetic modification while maintaining the ability to deliver reprogramming genes temporarily for direct reprogramming.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent employs short-lived RNA molecules as the delivery vehicle, which are degraded by the cell's natural RNA degradation pathways after serving their reprogramming function. This disposable RNA approach avoids the need for persistent viral or DNA vectors, eliminating long-term safety concerns while achieving the desired transient gene expression for direct reprogramming.

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

2Reliability

If RNA-based gene delivery is used to exclude infection and genetic modification risks, then safety is improved, but stability and conversion efficiency deteriorate

Engineering Contradiction:

Improvesafety from infection and genetic modificationVSAvoidstability of RNA

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent creates a composite RNA construct that combines multiple functional elements (promoter, ribosome binding site, coding sequence, and stability-enhancing modifications) into a single integrated molecule. This composite design improves RNA stability and translation efficiency while maintaining the safety advantages of RNA-based delivery, resolving the contradiction between stability and safety.

Inventive Principle:

Principle #40Composite materials

3Productivity

If conventional direct reprogramming protocols are used, then transcription factors can be introduced, but conversion efficiency remains low and physiological functionality is not achieved

Engineering Contradiction:

Improveconversion efficiencyVSAvoidphysiological functionality

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent optimizes multiple parameters of the RNA construct including promoter strength, ribosome binding site sequences, coding sequence modifications, and delivery methods to maximize translation efficiency and protein expression. These parameter changes result in high conversion efficiency and maintain physiological functionality of the reprogrammed cells.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses synthetic RNA copies of transcription factors that are engineered to be highly stable and efficiently translated. These artificial RNA copies serve as functional substitutes for traditional DNA-based approaches, achieving high conversion efficiency without the need for permanent genetic integration, thereby maintaining physiological functionality.

Inventive Principle:

Principle #26Copying

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

The three-dimensional RNA constructs induce direct reprogramming with high efficiency and stability, enabling successful conversion of somatic cells into target cell types while retaining physiological functionality and avoiding genetic modification risks.

Implementation Method 1

a three-dimensional RNA construct, in which one or two types of transcripts, each having a repeating unit sequence for the expression of a transcription factor, are mixed and self-assembled

Methodology Applied

Scientific EffectSelf-assembly: Self-Assembly

Implementation Method 2

a three-dimensional RNA construct, in which one or two types of transcripts, each having a repeating unit sequence for inhibiting the expression of a transcription factor, are mixed and self-assembled

Methodology Applied

Scientific EffectRNA interference:

Data Source

PatentUS20250002857A1Composition for inducing direct reprogramming comprising self-assembled RNA construct

Publication Date: 2025.01.02 UNIV OF SEOUL IND COOP FOUND

AI summary

The composition for inducing direct reprogramming of the present disclosure, which is formed by self-assembly of transcripts comprising, as a repeating unit sequence, mRNA for the expression of a transcription factor, or RNA for RNA interference to inhibit the expression of a transcription factor can induce direct reprogramming in a stable and efficient manner.