APES Nucleic Acid Enhances Recombinant Polypeptide Production

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Solution Overview

Problem

Current methods for producing recombinant proteins using animal cells face challenges in achieving high production efficiency, particularly due to the suppression of NfkBia expression, which affects the ability to produce proteins like antibodies effectively.

Innovation Solution

The use of APES (Antibody Production Enhancing Sequence) nucleic acid molecules, which bind to the NfkBia mRNA, suppress its expression, thereby enhancing the activity of NF-kappa B and increasing the production of recombinant polypeptides by promoting their transcription and translation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If NfkBia expression is maintained at normal levels, then cell proliferation control is maintained, but recombinant protein production efficiency is suppressed

Engineering Contradiction:

Improverecombinant protein production efficiencyVSAvoidcell proliferation control

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent changes the expression level parameter of NfkBia by introducing nucleic acid molecules that suppress its expression, thereby transforming the cellular state from normal proliferation control to enhanced recombinant protein production while maintaining cell viability

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses NF-kappa B as an intermediary factor that, when released from NfkBia inhibition, acts as a mediator to enhance the transcriptional activity of recombinant protein genes, thereby indirectly boosting production efficiency

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If NfkBia expression is suppressed to enhance NF-kappa B activity, then recombinant polypeptide production increases, but cellular immune response regulation may be affected

Engineering Contradiction:

Improverecombinant polypeptide productionVSAvoidimmune response regulation

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent applies local quality change by specifically suppressing NfkBia expression in the context of recombinant protein production cells, creating a localized effect that enhances production without globally disrupting immune regulation mechanisms in the organism

Inventive Principle:

Principle #3Local quality

Applied Scientific Principles

This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.

Function Achieved in This Case

This approach significantly increases the production efficiency of recombinant proteins by suppressing NfkBia expression, leading to higher levels of antibody production and improved cell growth and survival rates.

Implementation Method 1

APES (Antibody Production Enhancing Sequence) nucleic acid molecules, which bind to the NfkBia mRNA, suppress its expression

Methodology Applied

Scientific EffectBase pairing:

Data Source

PatentUS11905325B2Recombinant polypeptide production method

Publication Date: 2024.02.20 CHUGAI PHARMA CO LTD

AI summary

Provided is a method capable of producing a protein at a high level using a cultured animal cell, comprising culturing a cell that expresses APES (Antibody Production Enhancing Sequence) and into which a DNA encoding a desired polypeptide has been introduced, thereby producing the desired polypeptide. APES contains a nucleotide sequence related to nuclear factor κB inhibitor α (NfkBia) and has a function of decreasing the intracellular expression of NfkBia.