Reprogramming Protein Delivery via Cationic Lipid Polymers

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Solution Overview

Problem

Current methods for treating cancer, particularly brain tumors and breast cancer, face challenges in effectively converting cancer cells into normal cells, with existing compositions and proteins not adequately addressing the need for in vivo cell reprogramming for therapeutic efficacy.

Innovation Solution

The use of pharmaceutical compositions comprising protein transduction reagents non-covalently bound to reprogramming proteins such as Sox2, Oct4, and Nanog, which are administered to subjects to induce in vivo cell conversion, allowing for the transformation of cancer cells into normal cells or transient multipotent stem cells that differentiate into non-cancerous cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing compositions and proteins are used for cancer treatment, then some therapeutic effect is achieved, but in vivo cell reprogramming capability is insufficient

Engineering Contradiction:
Improvetherapeutic efficacyVSAvoidin vivo cell reprogramming capability
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent combines reprogramming proteins (Oct4, Sox2, Nanog) with protein transduction reagents into a single composite composition. This merging enables the delivery system to simultaneously provide both the reprogramming capability and the therapeutic effect, resolving the contradiction between reliable therapy and adaptive reprogramming function.

Inventive Principle:
Principle #5Merging (Combining)

Solution Approach 2:

The invention uses composite material structure where reprogramming proteins are non-covalently bound to cationic lipid polymers. This composite approach allows the composition to exhibit both the stability needed for reliable therapy and the functional versatility for in vivo cell reprogramming, addressing the technical contradiction.

Inventive Principle:
Principle #40Composite materials

2Object-generated harmful factors

If reprogramming proteins are administered to convert cancer cells, then tumorigenicity is reduced, but delivery efficiency to target cells is insufficient

Engineering Contradiction:
ImprovetumorigenicityVSAvoiddelivery efficiency
Core Design Contradiction:
Object-generated harmful factorsVSProductivity

Solution Approach 1:

The patent introduces protein transduction reagents as intermediary carriers that facilitate the delivery of reprogramming proteins to cancer cells. These cationic lipid polymer intermediaries enable efficient cellular uptake and intracellular delivery, resolving the contradiction between reducing tumorigenicity and achieving sufficient delivery efficiency.

Inventive Principle:
Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention modifies the physical and chemical parameters of the reprogramming proteins by non-covalent binding to cationic lipid polymers. This parameter change enhances cellular permeability and delivery efficiency while maintaining the biological function of the proteins to reduce tumorigenicity.

Inventive Principle:
Principle #35Parameter changes

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 the in vivo conversion of cancer cells into normal cells, reducing tumorigenicity and metastatic properties, as demonstrated by significant reductions in tumor volume, weight, and metastasis, along with prolonged survival in animal models, highlighting a novel and effective method for cancer treatment.

Implementation Method 1

a protein transduction reagent, which comprises a cation reagent and a lipid

Methodology Applied
Scientific EffectElectrostatic interaction: Electrostatic Induction

Data Source

PatentEP3060237B1Modified reprogramming protein for use in treating a cancer
Publication Date: 2021.08.18 QURGEN INC
  • EP3060237B1 patent drawingFigure 1A~1B
  • EP3060237B1 patent drawingFigure 2A~2C
  • EP3060237B1 patent drawingFigure 2D~2F

AI summary

Methods for treating a subject in need thereof are provided which include administering a pharmaceutical composition comprising a protein transduction reagent-modified reprogramming protein to the subject, wherein the protein transduction reagent is non-covalently bound to the reprogramming protein and wherein the protein transduction reagent comprises a cation reagent and a lipid. According to aspects, such methods provide delivery of protein-transduction reagent- modified reprogramming proteins to cancer cells, such as tumor cells, as well as diseased cells of diseased tissues and provide in vivo conversion of diseased cells into normal cells via protein- induced in situ cell reprogramming without administration of nucleic acids to the subject.