Hypoimmunogenic Stem Cells Evading Immune Rejection

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Solution Overview

Problem

Current regenerative medicine approaches using human pluripotent stem cells face immune rejection challenges due to immune responses, limiting the effectiveness of cell replacement therapies.

Innovation Solution

Development of hypoimmunogenic cells with reduced expression of MHC class I and II human leukocyte antigens and increased expression of CD24, along with genetic modifications targeting CIITA, B2M, and NLRC5 genes using rare-cutting endonucleases, to create cells that evade immune rejection.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If human pluripotent stem cells are used for cell replacement therapy, then the potential to treat most degenerative illnesses is improved, but immune rejection by the subject's immune response worsens

Engineering Contradiction:

Improvetreatment potentialVSAvoidimmune rejection

Core Design Contradiction:

Adaptability or versatilityVSObject-affected harmful factors

Solution Approach 1:

The patent applies parameter changes by genetically modifying stem cells to alter the expression levels of specific surface molecules. MHC class I and II expressions are reduced through genetic modification of CIITA and B2M genes, while CD24 expression is increased. This parameter modification of cell surface characteristics enables the cells to evade immune detection and rejection, resolving the contradiction between treatment versatility and immune rejection

Inventive Principle:

Principle #35Parameter changes

2Object-affected harmful factors

If HLA-matching strategies are used to overcome immune rejection, then immune compatibility is improved, but the complexity of finding matching donors and the need for immunosuppressive drugs worsens

Engineering Contradiction:

Improveimmune compatibilityVSAvoidtransplantation complexity

Core Design Contradiction:

Object-affected harmful factorsVSDevice complexity

Solution Approach 1:

Instead of matching the transplanted cells to the recipient's HLA type (conventional approach), the patent inverts the strategy by modifying the transplanted cells to have reduced HLA expression and increased CD24. This makes the cells universally compatible across different HLA backgrounds, eliminating the need for complex HLA-matching procedures and reducing reliance on immunosuppressive drugs

Inventive Principle:

Principle #13The other way round (Inversion)

3Object-affected harmful factors

If immunosuppressive drugs are administered to prevent rejection, then immune compatibility is improved, but the side effects and long-term health risks worsen

Engineering Contradiction:

Improveimmune compatibilityVSAvoiddrug side effects

Core Design Contradiction:

Object-affected harmful factorsVSObject-generated harmful factors

Solution Approach 1:

The patent converts the harmful immune recognition process into a benefit by exploiting the immune system's natural tolerance mechanisms. By reducing MHC expression and increasing CD24 (a molecule associated with stemness and immune privilege), the modified cells are mistakenly perceived as self or non-threatening by the immune system. This converts the immune system's usual rejection response into acceptance, eliminating the need for immunosuppressive drugs and their associated side effects

Inventive Principle:

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

Data Source

PatentUS20230025289A1CD24 expressing cells and uses thereof

Publication Date: 2023.01.26 SANA BIOTECHNOLOGY INC

AI summary

Disclosed herein are cells including cells expressing CD24 and related methods of their use and generation. In some embodiments, the cells disclosed herein do not express one or more MHC I and/or MHC II human leukocyte antigens. In some embodiments, the cells are hypoimmunogenic.