Biodegradable Nanoparticles for Non-Viral Stem Cell Gene Delivery

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Solution Overview

Problem

Current treatments for glioblastoma, particularly the median survival rate of 14.6 months, are ineffective due to the invasive nature of the disease and the presence of brain tumor initiating cells that contribute to treatment resistance, necessitating a novel therapeutic approach that targets these cells.

Innovation Solution

The use of biodegradable polymeric nanoparticles combined with freshly extracted adipose tissue-derived mesenchymal stem cells to non-virally engineer the cells to synthesize and release anti-tumor proteins, such as BMP4, which selectively targets and suppresses brain tumor initiating cells, while maintaining their migratory ability towards tumor cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If viral gene delivery is used to modify MSCs to deliver therapeutic proteins, then therapeutic protein delivery is achieved, but insertional mutagenesis and immunogenicity occur

Engineering Contradiction:

Improvetherapeutic protein deliveryVSAvoidinsertional mutagenesis and immunogenicity

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent uses biodegradable polymeric nanoparticles as an intermediary carrier system to deliver therapeutic genes to MSCs, replacing direct viral integration. The nanoparticles serve as a temporary, non-integrating vector that delivers genetic material through endocytosis, avoiding the harmful effects of viral insertion while maintaining therapeutic delivery capability.

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The patent substitutes the biological viral delivery mechanism with a synthetic polymeric nanoparticle system. Instead of using viral vectors that integrate into host genomes, the invention employs chemically synthesized biodegradable polymers that deliver genes through non-viral mechanisms, eliminating insertional mutagenesis and immunogenicity associated with viral proteins.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

2Reliability

If bone marrow-derived MSCs are used for therapy, then therapeutic effect is achieved, but limited availability and decreased effectiveness with donor age occur

Engineering Contradiction:

Improvetherapeutic effectVSAvoidcell availability

Core Design Contradiction:

ReliabilityVSQuantity of substance

Solution Approach 1:

The patent changes the source parameter of MSCs from bone marrow to adipose tissue, fundamentally altering the availability and characteristics of the cell source. Adipose tissue-derived MSCs exhibit enhanced proliferation capacity, higher surface marker expression, and resistance to oncogenic transformation, directly addressing the limitations of bone marrow-derived cells.

Inventive Principle:

Principle #35Parameter changes

3Quantity of substance

If adipose tissue-derived MSCs are used instead of bone marrow-derived MSCs, then cell availability and proliferation capacity improve, but need for non-viral delivery method to avoid harmful effects

Engineering Contradiction:

Improvecell availabilityVSAvoidinsertional mutagenesis and immunogenicity

Core Design Contradiction:

Quantity of substanceVSObject-affected harmful factors

Solution Approach 1:

The patent employs biodegradable polymeric nanoparticles as an intermediary delivery system that combines with adipose tissue-derived MSCs to achieve non-viral gene transfer. This intermediary approach enables the utilization of the superior characteristics of AMSCs while avoiding the harmful effects of viral delivery methods.

Inventive Principle:

Principle #24Intermediary (Mediator)

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 enhances the delivery of therapeutic proteins directly to tumor sites, potentially increasing survival rates and improving treatment efficacy by targeting resistant cancer cells, offering a safer and more effective alternative to viral gene delivery methods.

Implementation Method 1

biodegradable polymeric nanoparticles combined with freshly-extracted adipose tissue-derived mesenchymal stem cells to non-virally engineer the cells

Methodology Applied

Scientific EffectSelf-assembly: Self-Assembly

Data Source

PatentUS20230105186A1Nanoparticle Modification of Human Adipose-Derived Mesenchymal Stem Cells for Treating Brain Cancer and Other Neurological Diseases

Publication Date: 2023.04.06 JOHNS HOPKINS UNIVERSITY

AI summary

The presently disclosed subject matter provides compositions, methods, and kits for transfecting adipose-derived mesenchymal stem cells (AMSCs) in freshly extracted adipose tissue using nanoparticles comprising biodegradable polymers self-assembled with nucleic acid molecules. The presently disclosed subject matter also provides methods for treating a neurological disease in a patient in need thereof, the method comprising administering the AMSCs transfected with the nucleic acid molecules to the patient, wherein the nucleic acid molecules encode one or more bioactive molecules functional in the treatment of a neurological disease, particularly wherein the neurological disease is a brain tumor.