Genetically Modified Tissue Reducing MHC Expression
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Solution Overview
Problem
Current transplantation methods face challenges with graft rejection due to immunological incompatibility between the transplant and the recipient, often requiring harsh immunosuppressive drugs that come with severe side effects and increased risks of infections and tumors.
Innovation Solution
Genetically altered tissues expressing reduced levels of MHC I and MHC II molecules, combined with complement inhibitory molecules like CD46, CD55, and CD59, to promote immunological tolerance and reduce the need for immunosuppressive drugs.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If standard transplantation methods are used with allogeneic or xenogeneic tissue, then transplant availability increases, but graft rejection occurs due to immunological incompatibility
Solution Approach 1:
The patent applies parameter changes by genetically modifying the tissue to alter MHC molecule expression levels. Specifically, the tissue is engineered to express reduced levels of MHC class I and MHC class II molecules, which are the key parameters determining immunological recognition. This parameter modification allows allogeneic or xenogeneic tissue to be transplanted without triggering strong rejection responses, thus resolving the contradiction between transplant availability and graft acceptance.
Solution Approach 2:
The patent introduces complement inhibitory molecules (CD46, CD55, CD59) as intermediary protective factors. These molecules act as mediators between the transplant tissue and the recipient's immune system, specifically inhibiting the complement pathway that would otherwise be activated by immunological incompatibility. This intermediary mechanism protects the graft from rejection while maintaining the benefits of allogeneic or xenogeneic transplantation.
2Reliability
If immunosuppressive drugs are used to prevent graft rejection, then graft acceptance improves, but severe side effects and increased infection risk occur
Solution Approach 1:
The patent converts the harmful effect of immunological incompatibility into a benefit by genetically engineering the tissue to express reduced MHC molecules and complement inhibitory factors. Instead of using immunosuppressive drugs to mask the rejection problem, the invention modifies the tissue itself to become less immunogenic, thereby preventing rejection without the harmful side effects of immunosuppression.
Solution Approach 2:
The genetically modified tissue provides self-protection against rejection through its engineered characteristics. The tissue autonomously expresses reduced MHC molecules and complement inhibitory factors, making it inherently more compatible with the recipient's immune system without requiring external immunosuppressive intervention. This self-service approach eliminates the need for harmful immunosuppressive drugs.
3Reliability
If MHC molecules are completely eliminated from tissue, then immunological compatibility improves, but tissue function and recognition are compromised
Solution Approach 1:
The patent applies partial action by reducing rather than completely eliminating MHC molecule expression. The tissue is engineered to express reduced levels of MHC class I and MHC class II molecules, which is sufficient to improve immunological compatibility and reduce rejection responses, while maintaining enough MHC expression to preserve basic tissue function and cellular recognition processes.
Solution Approach 2:
The patent modifies the expression level parameter of MHC molecules to an optimal range that balances immunological compatibility with tissue functionality. By controlling the degree of MHC reduction and combining it with complement inhibitory factor expression, the invention achieves a parameter optimization that prevents rejection while maintaining normal tissue operations.
Data Source
AI summary
Tissue for use as a transplant, which tissue is allogeneic or xenogeneic and respectively the tissue may express an MHC I molecule that is immunologically incompatible to the transplant recipient and/or may express an MHC II molecule immunologically incompatible to the transplant recipient. The tissue suitable for use as a transplant and the method for its production include a genetic alteration of the tissue that provides for immunologic compatibility of the tissue with a transplant recipient. In the tissue for use as a transplant, which tissue expresses allogeneic or xenogeneic MHC I and/or allogeneic or xenogeneic MHC II molecules, the expression of the allogeneic or xenogeneic MHC I is downregulated by at least 50% to up to 90%, preferably the expression of the allogeneic or xenogeneic MHC I is downregulated by at least 60%.