5′/3′ UTR Selection for mRNA Translation and Stability

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Solution Overview

Problem

Existing mRNA-based therapeutics face challenges in achieving high translation efficiency and stability, which affect the dosage and clinical utility of mRNA medicaments, particularly mRNA vaccines.

Innovation Solution

Incorporation of specific 5'-UTRs and/or 3'-UTRs derived from various human genes, including PPIA, HPX, FTCD, CDK5RAP3, HSPA8, HBA1, HBB, MPND, FBXW10, FBXW12, PGLYRP1, and others, into recombinant RNA molecules to enhance translation efficiency and stability.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional UTRs are used in mRNA molecules, then the mRNA can be synthesized and translated, but the translation efficiency and stability are insufficient

Engineering Contradiction:

Improvetranslation efficiencyVSAvoidmRNA stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent applies parameter changes by selecting and optimizing specific UTR sequences from different genes (such as PPIA, HPX, FTCD, CDK5RAP3, HSPA8, HBA1, HBB, MPND, FBXW10, FBXW12, PGLYRP1) to achieve enhanced translation efficiency and mRNA stability. Different UTR sequences serve as different parameter configurations that improve the performance of mRNA molecules.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs composite materials by combining specific 5'-UTR and 3'-UTR sequences with the coding region of the gene of interest to create recombinant mRNA molecules. This composite structure integrates functional elements from different sources (UTRs from highly expressed genes + target gene coding region) to achieve superior translation efficiency and stability compared to natural mRNA.

Inventive Principle:

Principle #40Composite materials

2Productivity

If translation efficiency is increased to improve dosage, then the complexity of identifying optimal UTRs increases

Engineering Contradiction:

Improvetranslation efficiencyVSAvoidUTR identification complexity

Core Design Contradiction:

ProductivityVSDevice complexity

Solution Approach 1:

The patent applies preliminary action by pre-identifying and characterizing UTR sequences from genes with high expression levels (PPIA, HPX, FTCD, CDK5RAP3, HSPA8, HBA1, HBB, MPND, FBXW10, FBXW12, PGLYRP1) that have proven effectiveness. These pre-validated UTRs can be directly applied to various target genes without requiring de novo optimization for each application, thereby reducing complexity.

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

The patent demonstrates universality by showing that specific UTR sequences (from genes like PPIA, HPX, FTCD, etc.) can be universally applied across different target genes to enhance translation efficiency and stability. These UTRs serve as multi-functional elements that can be combined with various coding regions to achieve improved performance without requiring gene-specific optimization.

Inventive Principle:

Principle #6Universality (Multi-functionality)

Data Source

PatentEP4636090A1UTR for improving translation efficiency and/or stability of RNA molecule and use thereof

Publication Date: 2025.10.22 SHENZHEN SHENXIN BIOTECHNOLOGY CO LTD

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AI summary

Provided is a recombinant RNA molecule, which comprises a nucleotide sequence encoding a polypeptide of interest and 5'-UTR and/or 3'-UTR. The RNA molecule has improved translation efficiency and/or stability, and improves the expression level of a polypeptide and/or protein. Also provided are a vector encoding the recombinant RNA molecule, a pharmaceutical composition comprising the recombinant RNA molecule, and a method for treating or preventing a disease by using the recombinant RNA molecule.