PEG-PEI Conjugates for Gene Therapy Transfection

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Solution Overview

Problem

Current gene therapy methods face challenges in achieving efficient gene delivery due to issues such as low transfection efficiency, toxicity, and stability of nucleic acids, particularly with viral and non-viral vectors, where viral vectors have limitations like limited DNA carrying capacity, toxicity, and immunogenicity, while non-viral vectors struggle with lower efficiency and require optimization with cationic polymers like polyethyleneimine (PEI) that can be toxic at higher molecular weights.

Innovation Solution

Conjugation of polyethylene glycol (PEG) with polyethyleneimine (PEI) to form PEG-PEI conjugates, which are used to enhance the efficiency of viral and non-viral nucleic acid vector transfection by improving the stability and delivery of therapeutic polynucleotides, reducing toxicity, and increasing the viability of transfected cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If polyethyleneimine (PEI) is used to enhance transfection efficiency, then gene delivery efficiency is improved, but toxicity increases at higher molecular weights

Engineering Contradiction:

Improvetransfection efficiencyVSAvoidtoxicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the molecular weight parameter of PEI by conjugating it with PEG molecules of different sizes and ratios, transforming the original high-molecular-weight toxic PEI into a modified conjugate with optimized parameters that reduce toxicity while preserving transfection efficiency

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent creates a composite material by chemically conjugating polyethyleneimine with polyethylene glycol, combining the transfection-enhancing properties of PEI with the biocompatibility and low toxicity of PEG to produce a conjugate with superior overall performance

Inventive Principle:

Principle #40Composite materials

2Productivity

If viral vectors are used for gene delivery, then transfection efficiency is high, but immunogenicity and toxicity occur

Engineering Contradiction:

Improvetransfection efficiencyVSAvoidimmunogenicity

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent uses PEG-PEI conjugates as intermediary carriers that mediate gene delivery without directly using viral vectors, thereby achieving transfection efficiency comparable to viral methods while avoiding the immunogenicity and toxicity associated with viral-based approaches

Inventive Principle:

Principle #24Intermediary (Mediator)

3Object-affected harmful factors

If non-viral vectors are used for gene delivery, then toxicity is reduced, but transfection efficiency is low

Engineering Contradiction:

ImprovetoxicityVSAvoidtransfection efficiency

Core Design Contradiction:

Object-affected harmful factorsVSProductivity

Solution Approach 1:

The patent merges the advantages of both viral and non-viral approaches by creating a synthetic PEG-PEI conjugate that combines the low toxicity of non-viral vectors with enhanced transfection efficiency through optimized molecular structure and PEGylation, achieving a synergistic effect that surpasses conventional non-viral methods

Inventive Principle:

Principle #5Merging (Combining)

4Object-affected harmful factors

If PEG is conjugated to PEI to reduce toxicity, then biocompatibility is improved, but molecular weight and structure complexity increase

Engineering Contradiction:

ImprovetoxicityVSAvoidstructure complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

The patent segments the PEI structure by attaching PEG molecules at specific sites and ratios, creating a modular conjugate structure that can be systematically optimized by adjusting PEG chain length, number of PEG groups, and their distribution throughout the PEI framework

Inventive Principle:

Principle #1Segmentation

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 PEG-PEI conjugates significantly enhance the transfection efficiency and viability of cells, achieving at least 50% greater efficiency and viability compared to PEI alone, while reducing toxicity and improving the production of viral particles, making them suitable for treating genetic and infectious diseases.

Implementation Method 1

Conjugation of polyethylene glycol (PEG) with polyethyleneimine (PEI) to form PEG-PEI conjugates

Methodology Applied

Scientific EffectConjugation: Chemical Bonding

Data Source

PatentUS20230120141A1Polyethylene Glycol Conjugates of Polyethyleneimine and Their Use in Gene Therapy

Publication Date: 2023.04.20 CHARLES RIVER LABORATORIES INC

AI summary

The present invention is directed to improved methods for conjugating polyethylene glycol to polyethyleneimine, and to the use of such polyethylene glycol—polyethyleneimine conjugates to improve the efficiency with which viral and non-viral nucleic acid vectors transfect cells to provide gene therapy, and to improve the efficiency of producing viral particles that comprise therapeutic polynucleotides for use in gene therapy.