PEG-R9 siRNA Delivery System for Stable Circulation

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Solution Overview

Problem

Current gene therapy methods face challenges in achieving efficient gene delivery across cell membranes with minimal cytotoxicity and stability issues, particularly for siRNA delivery, due to problems with viral vectors, polymeric systems, and synthetic peptide-based delivery systems, which result in low transfection efficiency and instability in vivo.

Innovation Solution

A siRNA delivery system utilizing polyethylene glycol (PEG) and a nona-arginine (R9) peptide, where cysteine residues are attached to the R9 peptide, forming a PEG-R9 complex that enhances systemic circulation and transfection efficiency by forming stable, nano-sized complexes with siRNA, allowing for effective in vivo delivery.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If viral vectors are used for gene delivery, then transfection efficiency is improved, but immunogenicity and genetic recombination problems occur

Engineering Contradiction:

Improvetransfection efficiencyVSAvoidimmunogenicity and genetic stability

Core Design Contradiction:

ProductivityVSReliability

Solution Approach 1:

The patent uses PEG-R9 as an intermediary carrier between the siRNA and the cell membrane. This non-viral peptide complex acts as a mediator that facilitates gene delivery without triggering the immunogenicity and genetic recombination issues associated with viral vectors, while still achieving effective transfection.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention creates a composite delivery system by conjugating polyethylene glycol (PEG) with nona-arginine (R9) peptide to form PEG-R9. This composite material combines the stability and circulation properties of PEG with the cell-penetrating ability of R9, providing both safety and efficacy.

Inventive Principle:

Principle #40Composite materials

2Productivity

If synthetic peptide-based delivery systems are used, then endosomal escape is improved, but toxicity and serum instability occur

Engineering Contradiction:

Improveendosomal escape efficiencyVSAvoidtoxicity and serum instability

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent modifies the peptide structure by conjugating PEG to the R9 peptide, changing its physical and chemical parameters. This modification reduces toxicity and improves serum stability while preserving the endosomal escape capability of the original R9 peptide.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

PEG acts as a protective intermediary layer on the peptide surface, reducing direct interaction between the cationic peptide and cell membranes (lowering toxicity) while shielding the peptide from serum nucleases (improving stability).

Inventive Principle:

Principle #24Intermediary (Mediator)

3Productivity

If short cationic peptides are used for in vivo delivery, then delivery efficiency is improved, but nucleic acid stability and complex stability deteriorate

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidnucleic acid stability and complex stability

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The PEG-R9 composite provides both the delivery efficiency of cationic peptides and the stability of PEG. The conjugate forms stable complexes with siRNA while protecting them from degradation in the extracellular space.

Inventive Principle:

Principle #40Composite materials

4Stability of the object's composition

If lipids or liposomes are used for nucleic acid delivery, then complex stability is improved, but in vivo systemic circulation efficiency deteriorates

Engineering Contradiction:

Improvecomplex stabilityVSAvoidsystemic circulation efficiency

Core Design Contradiction:

Stability of the object's compositionVSProductivity

Solution Approach 1:

The patent replaces the lipid-based delivery system with a peptide-based system (PEG-R9). This substitution maintains complex stability through electrostatic interactions between the cationic peptide and anionic siRNA, while achieving superior systemic circulation due to the peptide's smaller size and lack of recognition by the reticuloendothelial system.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

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-R9 system significantly improves siRNA delivery efficiency and expression, with high transfection efficiency, low cytotoxicity, and extended circulation time, making it suitable for treating diseases such as cancer by effectively delivering siRNA to target cells.

Implementation Method 1

forming stable, nano-sized complexes with siRNA

Methodology Applied

Scientific EffectElectrostatic interaction: Electrostatics

Implementation Method 2

markedly improve the in vivo delivery efficiency of siRNA

Methodology Applied

Scientific EffectSteric protection:

Data Source

PatentUS9713645B2Short interference RNA gene delivery system for systemic circulation

Publication Date: 2017.07.25 INDUSTRY UNIVERSITY COOPERATION FOUNDATION HANYANG UNIVERSITY

AI summary

The present invention relates to a gene delivery system which improves siRNA delivery and the in vivo systemic circulation efficiency thereof More particularly, the present invention is a siRNA gene delivery system for systemic circulation based on polyethylene glycol (PEG) and an arginine 9 (R9) peptide.