Polypeptide siRNA Nanoparticles for HER2+ Cancer Targeting

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Solution Overview

Problem

Current methods for delivering RNAi and antisense therapeutics lack effective and targeted delivery vectors, limiting their application to localized treatments due to the absence of reasonably priced, non-toxic vectors for systemic or targeted delivery.

Innovation Solution

A treatment delivery platform comprising a polypeptide sequence adapted to target and penetrate specific cells, bound to a delivery molecule via electrostatic interactions, specifically using a HerPBK10 protein that facilitates the delivery of siRNA to HER2+ cancer cells through receptor binding and membrane penetration.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If localized administration methods are used for RNAi and antisense therapeutics, then delivery safety is improved, but treatment versatility deteriorates

Engineering Contradiction:
Improvedelivery safetyVSAvoidtreatment versatility
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent introduces a targeted delivery vector as an intermediary carrier that binds to the therapeutic agent (RNAi or antisense molecule) and transports it to the target cell. This vector mediates between the therapeutic agent and the target cell, enabling safe and effective delivery. The vector includes a targeting ligand that recognizes specific cell surface markers, ensuring selective delivery to diseased cells while sparing healthy tissue, thus resolving the contradiction between safety and versatility.

Inventive Principle:
Principle #24Intermediary (Mediator)

2Productivity

If non-specific delivery vectors are used, then delivery efficiency is improved, but targeting precision deteriorates

Engineering Contradiction:
Improvedelivery efficiencyVSAvoidtargeting precision
Core Design Contradiction:
ProductivityVSMeasurement precision

Solution Approach 1:

The patent applies local quality by equipping the delivery vector with a specific targeting ligand that confers selective binding capability to certain cell types. Different regions of the vector have different functions: the targeting ligand region provides specificity, while other regions provide delivery efficiency. This functional differentiation within the vector structure enables both high delivery efficiency and precise targeting simultaneously.

Inventive Principle:
Principle #3Local quality

Solution Approach 2:

The delivery vector is constructed as a composite structure combining multiple functional components: a targeting ligand (such as an antibody or peptide), a carrier molecule (such as a liposome or polymer), and the therapeutic payload. This composite design integrates the specificity of the ligand with the delivery efficiency of the carrier, resolving the contradiction between targeting precision and delivery efficiency.

Inventive Principle:
Principle #40Composite materials

3Reliability

If high doses of therapeutic agents are administered, then treatment effectiveness is improved, but off-target effects worsen

Engineering Contradiction:
Improvetreatment effectivenessVSAvoidoff-target effects
Core Design Contradiction:
ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The targeted delivery vector acts as a mediator that concentrates the therapeutic agent at the target site, allowing effective treatment with lower overall doses. By directing the agent specifically to diseased cells through receptor-ligand binding, the vector reduces the amount of agent needed while maintaining effectiveness and minimizing off-target exposure.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent applies local quality by concentrating the therapeutic effect locally at the target cell through specific ligand-receptor binding. This localized delivery ensures that high concentrations of the therapeutic agent are achieved only at the disease site, while systemic exposure remains low, thereby improving effectiveness without increasing off-target effects.

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

The platform enables targeted and efficient delivery of siRNA to HER2+ cancer cells, achieving significant gene knock-down and cell death while sparing non-target cells, with enhanced stability and reduced off-target effects.

Implementation Method 1

a delivery molecule bound to the polypeptide sequence via electrostatic interactions

Methodology Applied
Scientific EffectElectrostatic interactions: Electrostatics

Data Source

PatentUS11795454B2Targeted delivery system
Publication Date: 2023.10.24 CEDARS SINAI MEDICAL CENT
  • US11795454B2 patent drawing
  • US11795454B2 patent drawing
  • US11795454B2 patent drawing

AI summary

The present invention relates a targeted delivery system for siRNA or antisense technology. In one embodiment, the invention provides for a method of treating cancer by administering a therapeutically effective dosage of HerPBK10 combined with siRNA, resulting in the inhibition of Her2 expression and cell death. In another embodiment, a plurality of HerPBK10 combined with siRNA form a nanoparticle.