Modified mRNA Formulations for Protein Expression Without DNA Integration

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Solution Overview

Problem

Existing methods for delivering pharmaceutical compositions, such as modified nucleic acids, face challenges including integration into host cell genomic DNA, potential damage to cells, and inefficient protein expression due to multiple processing steps, particularly in primary cells or modified cell lines.

Innovation Solution

The development of modified mRNA (mmRNA) compositions formulated in saline or lipid formulations, such as liposomes and lipid nanoparticles, which are administered via various routes to enhance protein expression by minimizing immune response and improving intracellular retention.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If DNA is introduced into cells for protein expression, then protein production can be achieved, but DNA may integrate into host cell genomic DNA 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 production function from the DNA molecule itself and transfers it to mRNA molecules. By using mRNA directly as the delivery vehicle rather than DNA, the system achieves protein production without the risk of genomic integration and damage, as mRNA remains in the cytoplasm and does not integrate into host DNA.

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces mRNA as an intermediary between the genetic information and protein production. Instead of introducing DNA that must navigate the nucleus and risk integration, mRNA serves as a direct intermediary that can be translated in the cytoplasm, eliminating the harmful integration step while maintaining protein production capability.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If DNA is delivered to achieve protein expression, then therapeutic protein levels can be obtained, but multiple processing steps are required creating lag times and opportunities for error

Engineering Contradiction:

Improveprotein expression levelVSAvoidprocessing lag time

Core Design Contradiction:

ProductivityVSLoss of time

Solution Approach 1:

The patent extracts the protein production capability from the nuclear DNA pathway and relocates it to cytoplasmic mRNA. This eliminates the time-consuming steps of nuclear transport, transcription, and processing that DNA would require, allowing direct translation of mRNA to protein in the cytoplasm and significantly reducing lag time.

Inventive Principle:

Principle #2Taking out (Extraction)

3Productivity

If DNA is introduced into primary cells or modified cell lines, then protein expression can occur, but expression rates are frequently insufficient or not achieved at all

Engineering Contradiction:

Improveprotein expression rateVSAvoidexpression success rate

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent changes the fundamental parameter of the delivery molecule from DNA to mRNA. This parameter change is particularly effective in primary cells and modified cell lines because mRNA does not require nuclear import or transcriptional activation, directly addressing the low expression rates and failures associated with DNA delivery in these challenging cell types.

Inventive Principle:

Principle #35Parameter changes

Data Source

PatentUS12502431B2Delivery and formulation of engineered nucleic acids

Publication Date: 2025.12.23 MODERNATX INC

AI summary

Provided are formulations, compositions and methods for delivering biological moieties such as modified nucleic acids into cells to modulate protein expression. Such compositions and methods include the delivery of biological moieties, and are useful for production of proteins.