Dextran-peptide hybrid for gene delivery

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Solution Overview

Problem

Current gene delivery systems, particularly non-viral vectors, face challenges such as low transfection efficiency, high toxicity, and poor biocompatibility, limiting their effectiveness in gene therapy applications.

Innovation Solution

A novel composition of polysaccharide polymers with cationic peptides as nucleic acid delivery side chains, forming polysaccharide-nucleic acid complexes that facilitate efficient cellular uptake and transfection, while being biodegradable and biocompatible.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If non-viral vectors are used for gene delivery, then safety is improved by avoiding viral immunogenicity and mutagenesis, but transfection efficiency deteriorates compared to viral vectors

Engineering Contradiction:

ImprovesafetyVSAvoidtransfection efficiency

Core Design Contradiction:

ReliabilityVSProductivity

Solution Approach 1:

The patent uses composite materials by combining cationic peptides with natural polysaccharides (dextran, chitosan, hyaluronic acid) to create hybrid gene delivery vectors. This composite structure integrates the transfection efficiency enhancement from cationic peptides with the biocompatibility and safety of natural polysaccharides, resolving the contradiction between safety and transfection efficiency

Inventive Principle:

Principle #40Composite materials

Solution Approach 2:

The patent modifies the chemical parameters of natural polysaccharides by introducing cationic peptide sequences with specific amino acid compositions (arginine, lysine, histidine residues). These parameter changes enable the polysaccharides to condense nucleic acids effectively and facilitate endosomal escape, thereby improving transfection efficiency while maintaining the safety profile of natural materials

Inventive Principle:

Principle #35Parameter changes

2Productivity

If synthetic cationic materials are used to achieve high transfection efficiency, then transfection efficiency is improved, but toxicity increases and biocompatibility deteriorates

Engineering Contradiction:

Improvetransfection efficiencyVSAvoidtoxicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent changes the chemical composition parameters by using natural amino acids (arginine, lysine, histidine) instead of synthetic cationic materials. These natural amino acid-based cationic peptides achieve high transfection efficiency through electrostatic interaction with nucleic acids while being biodegradable and less cytotoxic, thus resolving the contradiction between transfection efficiency and toxicity

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent employs biodegradable cationic peptides that can be metabolized by cells after performing their delivery function. These peptides are designed to be transient and disposable, breaking down into harmless amino acids after facilitating gene transfection, thereby reducing long-term toxicity while maintaining high transfection efficiency

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Adaptability or versatility

If peptide size is increased to accommodate multiple functions (DNA condensation, endosomal escape, targeting), then functional versatility is improved, but cost increases dramatically

Engineering Contradiction:

Improvefunctional versatilityVSAvoidcost

Core Design Contradiction:

Adaptability or versatilityVSQuantity of substance

Solution Approach 1:

The patent segments the gene delivery functions by attaching separate functional cationic peptide sequences (for DNA condensation, endosomal escape, and targeting) to a natural polysaccharide backbone. This segmentation allows each peptide module to perform its specific function independently while sharing the common polysaccharide platform, reducing the overall cost compared to creating one large multifunctional peptide

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent creates universality by using a common natural polysaccharide backbone that can be conjugated with different cationic peptide sequences to achieve various delivery functions. The polysaccharide platform serves multiple purposes (structural support, biocompatibility, solubility) while the attached peptides provide specific functions, reducing the need for separate large peptides for each function

Inventive Principle:

Principle #6Universality (Multi-functionality)

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 polysaccharide-peptide hybrid system achieves high transfection efficiency, low cytotoxicity, and effective targeting, overcoming the limitations of existing non-viral vectors by forming stable complexes that enable efficient gene delivery.

Implementation Method 1

these cationic peptides condense and physically bond to one or more nucleic acids to form a polysaccharide-nucleic acid complex

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Data Source

PatentUS10058620B2Dextran-peptide hybrid for efficient gene delivery

Publication Date: 2018.08.28 THE UNIVERSITY OF AKRON

AI summary

One or more embodiments of the present invention provide a novel composition for gene delivery are directed to a group of polysaccharide polymers, having one or more nucleic acid delivery side chains comprising cationic peptides. In some embodiments, these cationic peptides condense and physically bond to one or more nucleic acids to form a polysaccharide-nucleic acid complex that permits delivery to and transfection of the nucleic acid(s) into cells. In some embodiments, the polysaccharide polymers of the present invention may also have one or more zwitterionic side chains and/or reactive side chains.