5' and 3' UTR Combinations for Stable mRNA Expression

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Solution Overview

Problem

Existing mRNA molecules are unstable and prone to degradation, limiting their effectiveness in gene therapy and other applications due to insufficient stability and protein expression levels.

Innovation Solution

The use of specific 5' and 3' UTR combinations, selected from sequences corresponding to SEQ ID NOs: 1-36, to enhance the stability and translation efficiency of mRNA molecules, thereby increasing protein expression levels.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Stability of the object's composition

If conventional mRNA molecules are used, then the basic translation function is achieved, but the mRNA is unstable and easy to be degraded by RNAase

Engineering Contradiction:

ImprovemRNA stabilityVSAvoidresistance to degradation

Core Design Contradiction:

Stability of the object's compositionVSReliability

Solution Approach 1:

The patent divides the mRNA molecule into functional segments, specifically identifying and optimizing the 5' UTR and 3' UTR regions. By segmenting the mRNA and analyzing each region's contribution to stability and translation, the invention can target specific segments for modification to enhance overall mRNA performance without affecting the entire molecule.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies local quality by introducing specific sequence characteristics at particular locations within the mRNA. The 5' UTR and 3' UTR are designed with specific nucleotide compositions and structures that locally enhance stability and translation efficiency. For example, the 5' UTR may contain specific stem-loop structures or GC-rich regions that protect against degradation while the 3' UTR contains polyadenylation signals and stability elements.

Inventive Principle:

Principle #3Local quality

2Productivity

If mRNA stability is improved through UTR sequences, then protein expression level increases, but the complexity of mRNA design increases

Engineering Contradiction:

Improveprotein expression levelVSAvoidmRNA sequence complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent develops universal 5' UTR and 3' UTR sequences that can be applied across different mRNA molecules. These universal elements perform multiple functions: enhancing translation efficiency, improving mRNA stability, and reducing degradation. By creating a library of tested and validated universal UTR sequences, the invention can quickly design stable mRNA molecules without redeveloping stability elements for each specific application.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Solution Approach 2:

The patent systematically varies key parameters of the UTR sequences, such as GC content, length, secondary structure features, and specific motif compositions. By changing these parameters and testing their effects, the invention identifies optimal parameter ranges that maximize protein expression while maintaining reasonable design complexity. For example, optimizing the GC content of the 5' UTR to enhance ribosome binding or adjusting the length of the 3' UTR polyA tail for maximum stability.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentEP4624574A1UTR molecule for increasing protein expression level

Publication Date: 2025.10.01 SUZHOU ABOGEN BIOSCIENCES CO LTD

Figure 1~2

AI summary

The present disclosure relates to a UTR molecule and use thereof. Specifically, the present disclosure relates to an mRNA molecule comprising 5' UTR and 3' UTR. The UTR molecule can significantly increase mRNA expression level.