Artificial mRNA 3′-UTR Poly(A) Design for Higher Protein Expression

Solution Overview

Problem

Current gene therapy and genetic vaccination methods using nucleic acid molecules face challenges such as genomic integration risks, limited expression levels, and instability of RNA, particularly due to degradation by RNases, which affect the efficacy of protein production and immune response induction.

Innovation Solution

Development of artificial nucleic acid molecules, specifically mRNA species, incorporating a 3′-UTR with a poly(A) sequence or polyadenylation signal, to enhance stability and translation efficiency, thereby improving protein production and immune response.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If natural nucleic acid molecules are used for gene therapy and genetic vaccination, then the methods can provide specific and individual treatment options, but the RNA is unstable and degraded by RNases, limiting efficacy

Engineering Contradiction:

Improvestability of nucleic acid moleculeVSAvoidRNA stability

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent modifies the nucleic acid molecule by changing the sequence parameters of the 3'-UTR region, specifically incorporating poly(A) sequences with defined lengths (50-400 adenine nucleotides) and polyadenylation signals. This parameter change in the nucleic acid structure enhances stability and reduces degradation by RNases, directly resolving the contradiction between reliability and RNA stability.

Inventive Principle:

Principle #35Parameter changes

2Productivity

If nucleic acid molecules are used to induce protein production, then gene therapy and genetic vaccination can be achieved, but the expression levels are limited, affecting efficacy

Engineering Contradiction:

Improveprotein production levelVSAvoidprotein quantity

Core Design Contradiction:

ProductivityVSQuantity of substance

Solution Approach 1:

The patent optimizes the 3'-UTR sequence parameters by incorporating specific poly(A) sequence lengths and polyadenylation signals, which enhances translation efficiency and protein production levels. This parameter optimization in the nucleic acid structure directly increases the quantity of protein produced, resolving the contradiction between productivity and protein quantity.

Inventive Principle:

Principle #35Parameter changes

3Reliability

If conventional nucleic acid molecules are used, then the methods are relatively simple, but genomic integration risks and RNA degradation occur, reducing therapeutic efficacy

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidgenomic integration risks and RNase degradation

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the nucleic acid molecule by changing the sequence parameters of the 3'-UTR region, specifically incorporating poly(A) sequences with defined lengths (50-400 adenine nucleotides) and polyadenylation signals. This parameter change in the nucleic acid structure enhances stability and reduces degradation by RNases, directly resolving the contradiction between reliability and RNA stability.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS20260071224A1Artificial nucleic acid molecules for improved protein expression

Publication Date: 2026.03.12 CUREVAC SE

AI summary

The invention relates to a method for stimulating an immune response by intramuscular injection of an artificial nucleic acid molecule comprising an open reading frame encoding an antigen and a 3′-UTR comprising at least two poly(A) sequences. The method may yield an increased immune response to the antigen or an increased neutralizing antibody response to the antigen.