Polymer-Encapsulated Viral Vectors for Targeted Gene Delivery
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Solution Overview
Problem
Current viral vector-based gene therapy and vaccination methods face challenges in targeted cell delivery, leading to nonspecific transduction and safety concerns due to the presence of envelope proteins, which can cause unintended cell transduction and immunogenicity.
Innovation Solution
Development of synthetic packaged viral vector nanoparticles coated with polymers, specifically poly(beta-amino ester) nanoparticles lacking envelope proteins, to enhance targeted delivery of genetic material for gene therapy and vaccine applications, utilizing oligopeptides for cellular uptake and targeting moieties for specific cell targeting.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If viral vectors with envelope proteins are used for gene delivery, then transduction efficiency is improved, but safety deteriorates due to unintended cell transduction and immunogenicity
Solution Approach 1:
The patent removes envelope proteins from viral vectors to eliminate the harmful effects of unintended transduction and immunogenicity. The extracted viral vectors are then encapsulated in polymer nanoparticles that provide controlled delivery without the harmful properties of envelope proteins, thereby resolving the contradiction between transduction efficiency and safety.
Solution Approach 2:
Polymer nanoparticles serve as an intermediary between the viral vector and target cells. The polymer coating mediates the delivery process, enabling controlled transduction while preventing the harmful interactions that envelope proteins cause with non-target cells and the immune system.
2Reliability
If viral vectors are used for targeted cell delivery, then gene therapy efficacy is improved, but specificity deteriorates due to nonspecific cell transduction
Solution Approach 1:
The patent applies local quality by functionalizing the polymer nanoparticle surface with specific ligands or targeting moieties at localized positions. This enables the viral vectors to recognize and bind to specific cell surface receptors on target cells, thereby achieving high specificity while maintaining transduction efficacy.
Solution Approach 2:
The patent changes the physical and chemical parameters of the delivery system by using polymer-encapsulated viral vectors instead of naked viral vectors. The polymer coating modifies surface charge, hydrophobicity, and steric properties, enabling improved cellular uptake and targeted delivery while reducing nonspecific transduction.
3Object-affected harmful factors
If polymer coating is applied to viral vectors, then safety and specificity are improved, but transduction efficiency may deteriorate due to potential interference with cellular uptake
Solution Approach 1:
The patent creates composite materials by combining viral vectors with polymer coatings. The composite structure integrates the high transduction capability of viral vectors with the safety and targeting properties of polymers, achieving both improved safety and maintained transduction efficiency through synergistic effects.
Solution Approach 2:
The patent optimizes polymer coating parameters such as thickness, charge density, and composition to balance safety and transduction efficiency. By carefully controlling these parameters, the polymer coating provides protection and specificity without creating a barrier that would prevent cellular uptake and transduction.
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 polymer-coated nanoparticles provide improved safety and specificity in transducing target cells, reducing unintended transduction and immunogenicity, while maintaining high transduction efficiency and stability, especially at low pH, thus enhancing the efficacy and safety of gene therapy and vaccine delivery.
Implementation Method 1
the polymer or the mixture of polymers comprises a poly(beta-amino ester) having the general formula wherein each Pep is an oligopeptide
Implementation Method 2
R is OH, CH3, or a cholesterol
Implementation Method 3
the sequence of the peptide is selected so as to promote cellular uptake and targeting of the polymer-coated vector
Implementation Method 4
maintaining high transduction efficiency and stability, especially at low pH
Data Source
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AI summary
The present technology relates to gene delivery vehicles comprising a retroviral vector coated with a polymer or a mixture of polymers to form a nanoparticle. The retroviral vectors comprise a transgene and in certain embodiments lack envelope protein. The technology includes a method of making the gene delivery vehicles and a method of treating a disease by administering the gene delivery vehicles.