Engineered Poly(A) Tail With miRNA Sites for Targeted mRNA Expression

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Solution Overview

Problem

Current mRNA delivery systems exhibit strong hepatotropism, leading to widespread accumulation in multiple organs, tissues, and cells, making it difficult to achieve specific expression in targeted organs, tissues, and cells, and resulting in significant side effects on non-targeted sites.

Innovation Solution

Integration of miRNA binding sites into the Poly(A) tail of mRNA molecules to enhance specificity and stability, allowing controlled expression in specific organs, tissues, and cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If mRNA is delivered by lipid-based carrier systems, then delivery effectiveness is improved, but specificity of expression in targeted organs is reduced

Engineering Contradiction:

Improvedelivery effectivenessVSAvoidspecificity of expression

Core Design Contradiction:

ReliabilityVSManufacturing precision

Solution Approach 1:

The patent introduces miRNA binding sites at specific locations within the mRNA structure (5'UTR, 3'UTR, or coding region) to create local regulatory elements. These sites enable tissue-specific expression by allowing miRNAs expressed in particular tissues to bind and regulate mRNA translation or stability, thereby achieving spatially differentiated expression patterns while maintaining effective delivery through lipid carriers.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The patent uses miRNA binding sites as intermediary elements that mediate between the delivered mRNA and tissue-specific miRNAs. These intermediary sites allow the mRNA to be selectively regulated by endogenous miRNAs in a tissue-specific manner, enabling precision control of gene expression without modifying the delivery system itself.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Manufacturing precision

If miRNA binding sites are integrated into mRNA, then specificity of expression is improved, but molecular structure complexity increases

Engineering Contradiction:

Improvespecificity of expressionVSAvoidmolecular structure complexity

Core Design Contradiction:

Manufacturing precisionVSDevice complexity

Solution Approach 1:

The patent designs miRNA binding sites that can be universally applied across different mRNA molecules and target multiple tissues simultaneously. By using conserved miRNA sequences and modular insertion strategies, the same binding site design can be adapted to various therapeutic mRNAs, reducing the overall complexity burden while achieving broad tissue-specificity coverage.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent divides the mRNA structure into functional segments (5'UTR, coding region, 3'UTR) and selectively places miRNA binding sites in specific segments. This segmentation allows for modular design where binding sites can be independently optimized and combined, managing molecular complexity through structured organization rather than random insertion.

Inventive Principle:

Principle #1Segmentation

3Object-affected harmful factors

If miRNA binding sites are added to mRNA, then off-target effects are reduced, but production complexity increases

Engineering Contradiction:

Improveoff-target effectsVSAvoidproduction complexity

Core Design Contradiction:

Object-affected harmful factorsVSEase of manufacture

Solution Approach 1:

The patent incorporates miRNA binding sites during the mRNA design and synthesis stage, before delivery. This preliminary integration ensures that tissue-specific regulation is built into the mRNA structure itself, allowing for straightforward production processes that don't require additional post-manufacturing steps. The binding sites are included in the initial transcription or synthesis process, simplifying overall manufacturing despite the enhanced specificity requirements.

Inventive Principle:

Principle #10Preliminary action

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 engineered Poly(A) tail with miRNA binding sites improves the specificity and stability of mRNA expression, enabling targeted delivery and reducing off-target effects, while facilitating large-scale production.

Implementation Method 1

miRNAs can bind to 3′ UTR of a target gene mRNA, and reduce the expression of the target gene by degradation or binding inhibition

Methodology Applied

Scientific EffectBase pairing:

Implementation Method 2

3′UTR is followed by a poly(A) sequence, which can prevent the degradation by an exonuclease

Methodology Applied

Scientific EffectPhysical protection:

Implementation Method 3

the Poly(A) tail sequence can also bind to a poly(A) binding protein (PABP), and further recruit many proteins such as eIF4G, eIF4B, and Paip-1 to form a complex

Methodology Applied

Scientific EffectProtein binding:

Data Source

PatentUS20260092293A1Expression-adjustable engineered RNA molecule

Publication Date: 2026.04.02 RINUAGENE BIOTECHNOLOGY CO LTD

AI summary

This application relates to an engineered RNA molecule, a DNA molecule encoding the engineered RNA molecule, and use of the engineered RNA molecule. The engineered RNA molecule comprises a Poly(A) tail sequence containing an miRNA binding site. The Poly(A) tail enables the accurate expression of a target gene in an organ, a tissue and/or a cell.