Cell-Penetrating Polypeptide Targeting via Extracellular DNA Binding

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Solution Overview

Problem

Current methods lack effective targeting of live cells, particularly those undergoing radiation or chemotherapy, due to limitations in cell-penetrating mechanisms, leading to inefficient delivery of therapeutic agents.

Innovation Solution

The use of cell-penetrating polypeptides that bind extracellular DNA to form complexes, allowing selective targeting and penetration of live cells at sites of interest, such as injuries or tumors, enhancing the delivery of therapeutic agents.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If cell-penetrating polypeptides are used to deliver therapeutic agents, then the delivery efficiency is improved, but the systemic toxicity increases

Engineering Contradiction:

Improvedelivery efficiencyVSAvoidsystemic toxicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The method induces cell death and releases extracellular DNA at the target site before administering the cell-penetrating polypeptide. This preliminary action creates a localized DNA-rich environment that attracts the polypeptide-therapeutic agent complex specifically to the target site, enabling efficient delivery while minimizing systemic exposure and toxicity

Inventive Principle:

Principle #10Preliminary action

Solution Approach 2:

Extracellular DNA acts as an intermediary that bridges the cell-penetrating polypeptide and the target cells. The polypeptide binds to extracellular DNA to form a complex that then interacts with live cells, facilitating selective penetration and delivery of therapeutic agents while reducing off-target effects

Inventive Principle:

Principle #24Intermediary (Mediator)

2Measurement precision

If cell-penetrating polypeptides bind extracellular DNA to form complexes, then the selective targeting of live cells is improved, but the complexity of the delivery system increases

Engineering Contradiction:

Improveselective targeting precisionVSAvoiddelivery system complexity

Core Design Contradiction:

Measurement precisionVSDevice complexity

Solution Approach 1:

The system utilizes the natural process of cell death and DNA release as a self-organizing mechanism. Dead cells automatically release extracellular DNA at the target site, which then spontaneously attracts the cell-penetrating polypeptide-therapeutic agent complex, eliminating the need for complex external targeting mechanisms while achieving high selective targeting precision

Inventive Principle:

Principle #25Self-service

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

This approach enables precise and efficient targeting of live cells, reducing systemic toxicity and increasing the effectiveness of therapeutic agents by facilitating their entry into cells, thereby improving treatment outcomes.

Implementation Method 1

the cell-penetrating polypeptide binds extracellular DNA near or around the live cells so as to form a complex or association therewith

Methodology Applied

Scientific EffectDNA binding:

Data Source

PatentUS20230077885A1Methods for DNA-dependent targeting of a cell permeant antibody

Publication Date: 2023.03.16 THE UNITED STATES OF AMERICA AS REPRESENTED BY THE DEPT OF VETERANS AFFAIRS

AI summary

The invention provides methods for selective targeting of live cells, which have undergone or are undergoing radiation or chemotherapy, at a site of interest with a cell-penetrating polypeptide. In one embodiment of the invention, the method comprises contacting the live cells with a cell-penetrating polypeptide comprising cell-penetrating determinants so that the cell-penetrating polypeptide binds extracellular DNA near or around the live cells so as to form a complex or association therewith such that the complex or associated polypeptide-DNA so bound bind the live cells and penetrates the live cells thereby selectively targeting live cells at a site of interest with a cell-penetrating polypeptide.