Genetically Modified Cells, Tissues and 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 immune responses, such as antibodies binding to tissues and cell-mediated immunity.
Innovation Solution
Genetically modify animals, particularly pigs, to reduce the expression of specific genes associated with immune rejection, such as MHC I-specific enhanceosome components, MHC I-binding peptide transporters, and complement component 3, and introduce exogenous polynucleotides encoding proteins like HLA-G and PD-L1 to suppress immune response.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If unmodified non-human animal tissues are used for transplantation, then the supply of transplantable organs and tissues is increased, but the tissues are rejected by the recipient's immune system
Solution Approach 1:
The patent applies parameter changes by genetically modifying the donor animal's cells to alter immune-related parameters. Specifically, it reduces or eliminates expression of non-human MHC class I molecules and NK cell ligands through genetic engineering, while simultaneously introducing human MHC class I molecules (HLA-G, HLA-E) and human leukocyte antigens. This parameter modification transforms the immunological profile of the graft to be more compatible with the human recipient, resolving the contradiction between increased supply and immune rejection.
Solution Approach 2:
The patent introduces human MHC class I molecules (HLA-G, HLA-E) and human leukocyte antigens as intermediary elements between the non-human donor tissue and the human recipient's immune system. These human antigens act as mediators that the recipient's immune system can recognize as self or tolerate, thereby reducing rejection. The intermediary human antigens bridge the immunological gap between species, allowing the non-human tissue to be accepted by the human immune system.
2Reliability
If genetically modified animals are used to reduce immune rejection, then graft survival is improved, but the complexity of the transplantation process increases
Solution Approach 1:
The patent applies preliminary action by performing genetic modifications on the donor animal's cells before transplantation. The genetic engineering to reduce non-human MHC class I expression and introduce human MHC class I molecules is completed in advance during animal breeding or cell culture, rather than during the transplantation procedure itself. This preliminary preparation of genetically modified donor cells simplifies the actual transplantation process while ensuring improved graft survival, as the immune compatibility is pre-established.
Data Source
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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.