Chimeric Retroviral-RNA Replicon Vector for Gene Delivery

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Solution Overview

Problem

Current lentiviral vectors do not provide high expression levels of proteins and fail to induce a robust inflammatory immune response, which is suboptimal for gene therapy and genetic immunization settings.

Innovation Solution

Development of a chimeric retroviral-RNA replicon vector particle with a retroviral envelope glycoprotein and an alphaviral replicon sequence, including a 5' untranslated region, sequence encoding an alphavirus replicase, and a heterologous nucleic acid sequence of interest, designed to enhance protein expression and immune activation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Ease of operation

If lentiviral vectors are used for targeted delivery of gene sequences, then delivery to non-dividing cells is achieved, but protein expression levels are low

Engineering Contradiction:

Improvedelivery capabilityVSAvoidprotein expression level

Core Design Contradiction:

Ease of operationVSProductivity

Solution Approach 1:

The patent combines lentiviral vector delivery mechanisms with alphavirus replicon expression systems to create a hybrid system that achieves both efficient delivery to non-dividing cells and high-level protein expression through replicon-mediated amplification

Inventive Principle:

Principle #5Merging (Combining)

Solution Approach 2:

The invention uses a composite vector system integrating lentiviral envelope proteins for cell entry with alphavirus replicon genomes for high-level expression, creating a hybrid vector that leverages strengths of both viral systems

Inventive Principle:

Principle #40Composite materials

2Ease of operation

If lentiviral vectors are used for gene delivery, then non-dividing cells are transduced, but inflammatory immune response is insufficient

Engineering Contradiction:

Improvetransduction capabilityVSAvoidimmune response strength

Core Design Contradiction:

Ease of operationVSObject-affected harmful factors

Solution Approach 1:

The patent merges lentiviral transduction efficiency with alphavirus immunogenicity to create a vector that both efficiently delivers genes to non-dividing cells and induces robust inflammatory immune responses for enhanced vaccination efficacy

Inventive Principle:

Principle #5Merging (Combining)

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 chimeric vector achieves high-level protein expression and induces a more inflammatory immune response, potentially leading to improved therapeutic outcomes in gene therapy and immunization.

Implementation Method 1

The replicase complex catalyzes cytoplasmic self amplification of the recombinant RNA

Methodology Applied

Scientific EffectRNA replication:

Data Source

PatentEP3374373B1A retroviral vector for the administration and expression of replicon RNA expressing heterologous nucleic acids

Publication Date: 2022.12.21 IMMUNE DESIGN CORP

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Figure 2A~2C

AI summary

The present disclosure relates generally to gene delivery using a chimeric, retroviral-RNA replicon vector particle for increased expression of transgenes in a host cell. In particular, the chimeric vectors described herein can be used in any of a variety of settings including gene therapy and vaccine settings.