Modified Macromolecule Transduction Domain for Cell Permeability

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Solution Overview

Problem

Conventional methods for delivering biologically active macromolecules, such as proteins and nucleic acids, across cell membranes face challenges due to low efficiency and stability, with existing peptides like PTDs and MTSs struggling to achieve effective intracellular delivery, especially in deep tissues, and often resulting in degradation within lysosomes.

Innovation Solution

A modified macromolecule transduction domain (MTD) with improved cell membrane permeability is developed by modifying the amino acid sequence, incorporating hydrophilic amino acids, and using chimeric fusion to enhance physical properties and delivery efficiency, allowing direct permeation through the cell membrane without endocytosis.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If conventional transduction methods (electroporation, liposome fusion, viral transfection) are used to deliver biologically active macromolecules into cells, then delivery can be achieved, but cell damage, immune system loss, and steric hindrance occur reducing delivery efficiency

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidcell damage and immune system loss

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the amino acid sequence parameters of the macromolecule transduction domain, specifically adjusting the ratio of basic amino acids and incorporating hydrophilic amino acids to optimize cell permeability while reducing immunogenicity and steric hindrance

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite transduction domain by fusing the modified MTD with the biologically active macromolecule, forming a hybrid structure that combines the permeability properties of the MTD with the functional properties of the target molecule

Inventive Principle:

Principle #40Composite materials

2Productivity

If conventional MTD peptides are used for macromolecule transduction, then cell membrane permeability is achieved, but delivery efficiency to deep tissues remains insufficient

Engineering Contradiction:

Improvedeep tissue delivery efficiencyVSAvoiddelivery stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent optimizes the physical and chemical parameters of the MTD by modifying amino acid sequences to enhance stability and penetration capability, achieving effective delivery to deep tissues while maintaining delivery reliability

Inventive Principle:

Principle #35Parameter changes

3Productivity

If PTDs and MTSs are used for intracellular delivery, then some delivery capability is achieved, but degradation within lysosomes occurs reducing effectiveness

Engineering Contradiction:

Improveintracellular delivery capabilityVSAvoidmolecule stability against degradation

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The modified MTD enables macromolecules to bypass endocytic pathways and avoid lysosomal degradation through direct membrane permeation, protecting the delivered molecules from premature degradation before they reach their intracellular targets

Inventive Principle:

Principle #10Preliminary action

4Ease of operation

If hydrophobic MTD sequences are used for membrane permeation, then cell permeability is achieved, but physical properties and availability decrease

Engineering Contradiction:

Improvecell permeabilityVSAvoidphysical properties and availability

Core Design Contradiction:

Ease of operationVSStability of the object's composition

Solution Approach 1:

The patent modifies the amino acid composition parameters by incorporating hydrophilic amino acids and adjusting the basic amino acid ratio, transforming the MTD from highly hydrophobic to a balanced amphipathic structure that maintains cell permeability while improving physical properties and availability

Inventive Principle:

Principle #35Parameter changes

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

The modified MTD achieves significantly higher cell permeability and maintains the activity of delivered biologically active molecules, enabling effective intracellular delivery and deep tissue penetration, surpassing the limitations of conventional methods.

Implementation Method 1

Methodology Applied

Scientific EffectCell membrane permeation: Permeation

Data Source

PatentUS9694087B2Development of novel macromolecule transduction domain with improved cell permeability and method for using same

Publication Date: 2017.07.04 PROCELL THERAPEUTICS

AI summary

The present invention relates to an improved macromolecule transduction domain (MTD), which facilitates permeating the cell membrane of a biologically active molecule, having enhanced cell permeability. Specifically, an improved MTD according to the present invention, compared to an existing MTD, can transmit various types of biologically active molecule from inside the body and inside a test tube more effectively, and thus can be effectively used in a method to genetically alter a biologically active molecule so as to have cell permeability or in a method to transport a biologically active molecule into a cell, or the like. Additionally, the improved MTD can be very useful in development of new drugs and incrementally modified drugs as uses of the improved MTD are possible in drug delivery systems, recombinant protein vaccines or DNA/RNA therapeutic agents, gene or protein therapies, and pharmacologically or medically useful protein production or medical, pharmacological and pharmaceutical compositions.