Modified RNA G/C Content Jet Injection Expression

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Solution Overview

Problem

Current RNA-based gene therapy and genetic vaccination methods face challenges due to the instability of mRNA, leading to limited protein expression and the need for repetitive administrations, as well as inefficient delivery of RNA into cells, which hampers therapeutic effectiveness.

Innovation Solution

A modified RNA with increased G/C content in its coding region is administered via jet injection, enhancing protein expression by modifying the G/C content compared to its wild-type counterpart, and utilizing jet injection to improve delivery efficiency.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If RNA is administered by conventional injection methods, then delivery is possible, but delivery efficiency is insufficient

Engineering Contradiction:
Improvedelivery efficiencyVSAvoiddelivery method complexity
Core Design Contradiction:
ProductivityVSEase of operation

Solution Approach 1:

The patent changes the physical parameters of RNA delivery by modifying G/C content in the coding region, which alters the structural and stability properties of the RNA molecule, thereby improving delivery efficiency and protein expression without changing the amino acid sequence

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent performs preliminary modification of the RNA sequence by optimizing G/C content before administration, which pre-enhances the stability and expression characteristics of the RNA, leading to improved therapeutic effectiveness without requiring complex delivery procedures

Inventive Principle:
Principle #10Preliminary action

2Productivity

If unmodified RNA is used, then administration is straightforward, but protein expression is limited and duration is short

Engineering Contradiction:
Improveprotein expression levelVSAvoidRNA modification complexity
Core Design Contradiction:
ProductivityVSDevice complexity

Solution Approach 1:

The patent modifies the G/C content parameter in the RNA coding region while maintaining the same amino acid sequence, which enhances protein expression levels and duration without altering the fundamental function or structure of the encoded protein

Inventive Principle:
Principle #35Parameter changes

Solution Approach 2:

The patent applies localized modification only to the coding region's G/C content rather than modifying the entire RNA molecule, which improves expression while maintaining simplicity in other regions of the RNA structure

Inventive Principle:
Principle #3Local quality

3Duration of action of moving object

If RNA is administered without G/C content optimization, then sequence is simple, but protein expression duration is limited

Engineering Contradiction:
Improveprotein expression durationVSAvoidsequence modification complexity
Core Design Contradiction:
Duration of action of moving objectVSDevice complexity

Solution Approach 1:

The patent optimizes the G/C content parameter in the coding region to enhance the temporal duration of protein expression, extending the therapeutic effect without requiring complex structural modifications to the RNA molecule

Inventive Principle:
Principle #35Parameter changes

Data Source

PatentEP3036330B1Method for increasing expression of RNA-encoded proteins
Publication Date: 2018.09.12 CUREVAC SE
  • EP3036330B1 patent drawingFigure 1
  • EP3036330B1 patent drawingFigure 2
  • EP3036330B1 patent drawingFigure 3

AI summary

The invention relates to an RNA comprising at least one open reading frame (ORF) and comprising at least one modification, which increases the expression of the encoded peptide or protein. Furthermore, the invention relates to the medical use of such a modified RNA administered to a subject by jet injection. The invention relates further to a pharmaceutical composition and to a kit of parts comprising said modified RNA for administration by jet injection, preferably for use in the field of gene therapy and/or genetic vaccination. Additionally, the invention relates to a method for enhancing the (localized) expression of RNA-encoded peptides or proteins in the dermis or muscle (of a mammal) comprising administering the modified RNA by jet injection. And finally, the invention relates to a method of treatment comprising administering the modified RNA by jet injection to a subject in need thereof.