Hematopoietic Cells Knocked Out of CRL5 Genes for Anti-Tumor Therapy

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Solution Overview

Problem

The potency of T-cells and NK cells, crucial for anti-tumor immunity, is often limited by cellular dysfunction and exhaustion induced by the hostile tumor microenvironment, leading to reduced persistence and function upon infusion into a human subject.

Innovation Solution

Genetically modified hematopoietic cells with inhibited expression or activity of polypeptide products encoded by CRL5 complex-independent genes and CRL5 complex genes, using genetic modification systems such as CRISPR, TALEN, or shRNA, to enhance proliferation and resistance to immunosuppression.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If T-cells and NK cells are used for adoptive cell therapy, then anti-tumor immunity is enhanced, but cellular dysfunction and exhaustion occur due to the hostile tumor microenvironment

Engineering Contradiction:

Improveanti-tumor immunityVSAvoidcellular function

Core Design Contradiction:

ReliabilityVSStability of the object's composition

Solution Approach 1:

The patent extracts and removes specific genes (CRL5 complex genes and CRL5 complex-independent genes) from the hematopoietic cells that are responsible for cellular dysfunction and exhaustion. By knocking out these specific genes while preserving the overall cell structure and function, the invention eliminates the harmful effects of the tumor microenvironment without compromising the anti-tumor immunity of the adoptive cell therapy.

Inventive Principle:

Principle #2Taking out (Extraction)

2Productivity

If genetic modifications are made to inhibit CRL5 complex genes and CRL5 complex-independent genes, then proliferative capacity and resistance to immunosuppression are improved, but cellular structure and function are altered

Engineering Contradiction:

Improveproliferative capacityVSAvoidcellular structure

Core Design Contradiction:

ProductivityVSStability of the object's composition

Solution Approach 1:

The patent applies local quality by making specific, targeted genetic modifications to particular genes (CRL5 complex genes and CRL5 complex-independent genes) rather than altering the entire cellular structure. This localized approach allows the invention to improve proliferative capacity and resistance to immunosuppression in specific cellular pathways while preserving the overall stability and essential functions of the hematopoietic cell structure.

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20250032546A1Genetically modified cells and methods of making and using same

Publication Date: 2025.01.30 AUDAX BIOSCIENCES PTY LTD

AI summary

Provided herein are genetically modified hematopoietic cells with reduced expression or activity of: (i) one or more CRL5 complex genes, and/or (ii) one or more genes orthogonal to the CRL5 complex, that exhibit improved therapeutic potential compared to wild-type hematopoietic cells, as well as methods of generating and using genetically modified hematopoietic cells for the treatment of a disease, such as cancer.