Polymer-Encapsulated Viral Vectors for Gene Therapy

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Solution Overview

Problem

Current viral vector-based gene therapy methods face challenges in targeted delivery, immunogenicity, and safety due to the difficulty in precise cell targeting and accumulation in undesired tissues, leading to potential immune responses and hepatotoxicity.

Innovation Solution

Development of polymer-encapsulated viral vector nanoparticles with a poly(beta-amino ester) polymer shell, lacking viral fusion proteins, which naturally tropism to peripheral blood cells, reducing immunogenicity and improving safety by avoiding pseudotyping and viral spike proteins.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Productivity

If viral vectors are used for gene delivery, then transduction efficiency is improved, but immunogenicity and safety worsen due to pseudotyping proteins and spike proteins

Engineering Contradiction:

Improvetransduction efficiencyVSAvoidimmunogenicity

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent removes viral fusion proteins (pseudotyping proteins like VSV-G) from the vector surface, extracting the harmful immunogenic elements while retaining the essential gene delivery function through polymer encapsulation

Inventive Principle:

Principle #2Taking out (Extraction)

Solution Approach 2:

The patent introduces poly(beta-amino ester) polymer shells as intermediary structures that replace viral fusion proteins, mediating cell interaction and entry without triggering immune responses associated with viral spike proteins

Inventive Principle:

Principle #24Intermediary (Mediator)

2Productivity

If viral vectors are used for gene delivery, then transduction capability is improved, but safety worsens due to accumulation in undesired organs and tissues

Engineering Contradiction:

Improvetransduction capabilityVSAvoidorgan accumulation

Core Design Contradiction:

ProductivityVSObject-generated harmful factors

Solution Approach 1:

The patent confers specific tissue tropism properties to the polymer-encapsulated vectors, enabling them to preferentially target peripheral blood cells and lymphoid tissues while avoiding accumulation in undesired organs through controlled surface properties and natural tropism

Inventive Principle:

Principle #3Local quality

3Ease of operation

If pseudotyped viral vectors are used, then targeting capability is improved, but safety worsens due to immune response development

Engineering Contradiction:

Improvetargeting capabilityVSAvoidsafety profile

Core Design Contradiction:

Ease of operationVSReliability

Solution Approach 1:

The patent employs non-immunogenic polymer shells that do not trigger long-lasting immune responses, allowing repeated administrations without the safety concerns associated with pseudotyping proteins that elicit durable immune memory

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

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-encapsulated nanoparticles provide enhanced safety and efficacy by allowing targeted gene delivery without pseudotyping, reducing immune activation and hepatotoxicity, and avoiding accumulation in spleen, bone marrow, or liver, while maintaining effective transduction of desired cells.

Implementation Method 1

Viral vector nanoparticles of the present technology include an outer shell containing a poly(beta-amino ester) polymer which encapsulates the vector

Methodology Applied

Scientific EffectPolymer encapsulation:

Implementation Method 2

The polymer shell of the vector nanoparticles allows them to transduce cells without the need for pseudotyping or the inclusion of any viral fusion protein

Methodology Applied

Scientific EffectEndosomal uptake:

Implementation Method 3

The polymer shell of the vector nanoparticles allows them to transduce cells without the need for pseudotyping or the inclusion of any viral fusion protein, such as VSV-G

Methodology Applied

Scientific EffectMembrane fusion:

Implementation Method 4

The polymer molecules are end-modified with positively charged or negatively charged oligopeptides

Methodology Applied

Scientific EffectOligopeptide modification:

Implementation Method 5

Absence of spike proteins makes it possible for the OM-PBAE to form a complete, uninterrupted shell, thereby simplifying control over targeting, reducing immunogenicity, and improving the safety profile

Methodology Applied

Scientific EffectImmune evasion:

Implementation Method 6

The method includes providing a viral vector nanoparticle that contains a viral vector lacking a viral fusion protein and encoding the transgene; and a plurality of oligopeptide modified poly(beta amino ester) (OM-PBAE) molecules forming a shell surrounding the lentiviral vector

Methodology Applied

Scientific EffectViral transduction:

Implementation Method 7

cells of the subject are transduced by the viral vector and the transgene is expressed in the cells

Methodology Applied

Scientific EffectGene expression:

Data Source

PatentUS20220403416A1Polymer-Encapsulated Viral Vectors for In Vivo Genetic Therapy

Publication Date: 2022.12.22 IXAKA FRANCE

AI summary

Polymer-encapsulated viral vector nanoparticles and methods of using them provide enhanced delivery of genetic material for use in gene therapy and other applications. The nanoparticles include an outer shell containing an oligopeptide-modified poly(beta-amino ester) polymer which encapsulates the vector and allows the vector to transduce cells without the need for pseudotyping or the inclusion of any viral fusion protein, such as VSV-G. The polymer-encapsulated vector nanoparticles have a natural tropism for peripheral blood cells, such as leucocytes, without the need for a targeting moiety, and have an improved safety profile compared to pseudotyped viral vectors.