In Vivo CAR Expression Using Lipid Vectors and Immune-Specific Promoters

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Solution Overview

Problem

The complexity, labor intensity, and costs associated with cellular engineering methods have limited the number of patients who can benefit from chimeric antigen receptor (CAR)-T therapy.

Innovation Solution

A system for in vivo delivery of an expression construct encoding a heterologous immune receptor using a non-viral lipid-based delivery vector (LDV) and a polynucleotide driven by an immune cell-specific promoter, such as CD3, CD4, dLck, or NKp46, to facilitate efficient expression of CARs in immune cells.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If cellular engineering methods are used to generate CAR-T therapy, then CAR expression can be achieved in immune cells, but the complexity, labor intensity, and costs increase significantly

Engineering Contradiction:

ImproveCAR expressionVSAvoidcellular engineering complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent replaces complex mechanical cellular engineering processes (ex vivo manipulation, viral transduction, cell culture) with a simpler in vivo chemical/genetic approach using lipid-based delivery vectors that directly introduce expression constructs into immune cells within the patient's body, eliminating the need for sophisticated cellular manipulation facilities and procedures

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent extracts the essential function of CAR generation from the complex cellular engineering process and isolates it into a simplified in vivo delivery system using lipid-based vectors, separating the core function (CAR expression) from the complicating factors (ex vivo manipulation, viral vectors, cell culture infrastructure)

Inventive Principle:

Principle #2Taking out (Extraction)

2Reliability

If cellular engineering methods are used to generate CAR-T therapy, then CAR expression can be achieved in immune cells, but the labor intensity and costs increase

Engineering Contradiction:

ImproveCAR expressionVSAvoidmanufacturing simplicity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent replaces labor-intensive mechanical cellular engineering operations with automated or simplified in vivo delivery processes using lipid-based vectors, reducing the need for skilled laboratory personnel and complex manufacturing infrastructure while maintaining CAR expression effectiveness

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Solution Approach 2:

The patent employs disposable lipid-based delivery vectors that can be easily synthesized and administered, replacing expensive, complex, and reusable cellular engineering infrastructure, thereby reducing overall manufacturing costs and increasing accessibility

Inventive Principle:

Principle #27Cheap short-living objects (Disposable)

3Productivity

If conventional delivery vectors are used, then gene delivery can be achieved, but viral vectors pose safety concerns and non-viral vectors have limited efficiency

Engineering Contradiction:

Improvegene delivery efficiencyVSAvoidviral safety concerns

Core Design Contradiction:

ProductivityVSObject-affected harmful factors

Solution Approach 1:

The patent converts the potential harm of viral vectors (safety concerns, immunogenicity) into a benefit by using non-viral lipid-based vectors that avoid these problems while achieving comparable or superior delivery efficiency through optimized lipid composition and formulation, turning a harmful approach into a safe and effective one

Inventive Principle:

Principle #22Blessing in disguise (Convert harm into benefit)

Solution Approach 2:

The patent changes the fundamental parameters of the delivery vector from viral-based to non-viral lipid-based systems, altering the chemical and physical properties to achieve safe and efficient gene delivery without the harmful characteristics of viral vectors, thereby improving the risk-benefit ratio

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 streamlines the treatment process, improves accessibility, and reduces costs by enabling efficient and targeted expression of CARs in immune cells, potentially benefiting more patients with conditions like cancer.

Implementation Method 1

a non-viral lipid-based delivery vector (LDV)

Methodology Applied

Scientific EffectLipid-based delivery:

Data Source

PatentUS20260034241A1Compositions and methods for in vivo expression of chimeric antigen receptors

Publication Date: 2026.02.05 ONCOSENX INC

AI summary

Provided herein are compositions, systems, and methods suitable for in vivo delivery of CAR-encoding expression constructs. Expression constructs engineered to express a heterologous immune receptor under control of an immune cell-specific promoter are described (for example, to express a CAR under control of a T cell-specific promoter). The expression constructs can be used in combination with a lipid-based delivery vector (LDV) delivery system that facilitates effective delivery and repeat dosing.