Modified mRNA Molecules for Protein Expression

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Solution Overview

Problem

Current methodologies for protein expression using DNA face challenges such as integration into host cell genomic DNA, immunogenicity, low translation rates, and difficulties in delivering and processing nucleic acids effectively, leading to inefficiencies and errors in protein production.

Innovation Solution

Development of modified mRNA (mmRNA) molecules with structural and chemical features that optimize formulation, delivery, and expression, reducing immunogenicity and improving translation efficiency, stability, and protein production rates while avoiding immune responses and degradation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If DNA is introduced into host cells for protein expression, then protein production is achieved, but integration into host cell genomic DNA occurs causing alterations and damage

Engineering Contradiction:

Improveprotein productionVSAvoidgenomic DNA damage

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent extracts the protein expression function from DNA and relocates it to mRNA molecules. The mRNA carries the genetic code directly to ribosomes for translation, eliminating the need for DNA integration into host genomic DNA while maintaining protein production capability

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces mRNA as an intermediary carrier between the genetic code and protein synthesis. This intermediary allows protein expression without requiring permanent DNA integration, thus preventing genomic DNA damage while enabling sustained protein production

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If DNA is introduced into host cells, then protein expression can occur, but multiple processing steps create lag times and opportunities for error

Engineering Contradiction:

Improveprotein expression efficiencyVSAvoidprocessing lag time

Core Design Contradiction:

ProductivityVSLoss of time

Solution Approach 1:

The patent performs preliminary transcription of DNA into mRNA in vitro before introduction into host cells. This pre-processing eliminates the need for intracellular transcription steps, reducing processing time and minimizing opportunities for error while maintaining the complete protein expression pathway

Inventive Principle:

Principle #10Preliminary action

3Productivity

If standard mRNA is used for protein expression, then translation occurs, but immunogenicity and low translation rates limit effectiveness

Engineering Contradiction:

Improvetranslation rateVSAvoidimmunogenicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies mRNA parameters by incorporating pseudouridine and 5-methylcytosine nucleosides instead of standard nucleosides. These chemical modifications reduce immunogenicity recognition by the host immune system while enhancing translation efficiency and protein expression rates

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite mRNA structure combining modified nucleosides (pseudouridine and 5-methylcytosine) with standard nucleotide sequences. This composite approach maintains the genetic coding function while adding protective and enhancing properties that reduce immunogenicity and improve translation

Inventive Principle:

Principle #40Composite materials

Data Source

PatentUS10501512B2Modified polynucleotides

Publication Date: 2019.12.10 MODERNATX INC

AI summary

The invention relates to compositions and methods for the preparation, manufacture and therapeutic use of polynucleotides, primary transcripts and mmRNA molecules.