Genetically Modified Pig Organs for Reduced Immune Rejection

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Solution Overview

Problem

There is a shortage of organs, tissues, or cells available for transplantation, and unmodified non-human animal tissues are often rejected by the immune system of recipients due to antibody binding and cell-mediated immunity.

Innovation Solution

Genetically modify non-human animals, such as pigs, to reduce the expression of specific genes associated with immune rejection, and introduce exogenous polynucleotides encoding proteins that suppress immune response, creating cells, tissues, or organs that can be transplanted with reduced immune rejection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Quantity of substance

If unmodified non-human animal tissues are used for transplantation, then the supply of transplantable materials is increased, but the tissues are rejected by the recipient's immune system due to antibody binding and cell-mediated immunity

Engineering Contradiction:

Improvesupply of transplantable materialsVSAvoidimmune rejection

Core Design Contradiction:

Quantity of substanceVSReliability

Solution Approach 1:

The patent applies parameter changes by genetically modifying the properties of non-human animal tissues through gene knockout and gene addition. Specific genes (GGTA1, CMAH, B4GALNT2) are knocked out to alter carbohydrate structures on cell surfaces, and human genes (HLA-G, PD-L1, PD-L2, CD47) are added to modify immune recognition parameters. These genetic parameter changes enable non-human animal tissues to resist immune rejection while maintaining their transplantable supply.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent uses human leukocyte antigen G (HLA-G) as an intermediary molecule that mediates between non-human animal tissues and the human immune system. HLA-G expression on transplanted tissues acts as a protective intermediary that suppresses natural killer cell activity and modulates T cell responses, thereby reducing immune rejection of xenotransplanted materials.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If genetically modified non-human animals are created to reduce immune rejection, then immune compatibility is improved, but the complexity of production and genetic modification increases

Engineering Contradiction:

Improveimmune compatibilityVSAvoidgenetic modification complexity

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent segments the immune compatibility problem into multiple discrete genetic targets. Instead of attempting a single complex modification, the invention knocks out specific genes (GGTA1, CMAH, B4GALNT2) individually and adds specific human genes (HLA-G, PD-L1, PD-L2, CD47) separately. This segmentation of genetic modifications makes the complex process more manageable and systematic.

Inventive Principle:

Principle #1Segmentation

Solution Approach 2:

The patent applies preliminary action by creating genetically modified non-human animal models (pigs, cows, sheep) before transplantation. The gene knockouts and gene additions are performed in advance during animal breeding and tissue cultivation, so that when tissues are harvested for transplantation, they already possess the desired immune-compatible properties without requiring complex modifications at the transplantation stage.

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS12465029B2Genetically modified cells, tissues, and organs for treating disease

Publication Date: 2025.11.11 REGENTS OF THE UNIVERSITY OF MINNESOTA

AI summary

Genetically modified cells, tissues, and organs for treating or preventing diseases are disclosed. Also disclosed are methods of making the genetically modified cells and non-human animals.