CRISPR-Edited Hypoimmunogenic Cells for Universal Transplantation
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Solution Overview
Problem
The availability of cell lines suitable for therapeutic applications is limited, and existing cell lines are not universally histo-compatible with all recipients, posing a challenge for effective blood and tissue transplantation.
Innovation Solution
The use of CRISPR-Cas9 gene editing to introduce deleterious variations in the ABO, RHD, and FUT1 genes to generate isolated cells with specific histo-blood types, such as histo-blood type O or Rh negative cells, which are hypoimmunogenic and universally compatible, reducing immune rejection.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If cell lines are used for therapeutic applications, then cell therapy can be provided, but immune rejection occurs due to histo-blood type incompatibility between donor and recipient
Solution Approach 1:
The patent applies parameter changes by modifying the histo-blood type characteristics of cells through CRISPR-Cas9 gene editing. Specifically, it inactivates the ABO gene to eliminate A and B antigens, inactivates the RHD gene to eliminate Rh(D) antigen, and inactivates the FUT1 gene to eliminate H antigen. These genetic parameter changes create cells with universal histo-blood type compatibility, resolving the immune rejection problem while maintaining therapeutic efficacy
Solution Approach 2:
The patent extracts and removes the immunogenic antigens from cell surfaces by targeting and inactivating the genes responsible for their production. By using CRISPR-Cas9 to delete or disrupt the ABO, RHD, and FUT1 genes, the patent effectively takes out the harmful antigenic determinants that cause immune rejection, leaving behind cells that are hypoimmunogenic and universally compatible
2Adaptability or versatility
If cell lines with specific histo-blood types are used, then compatibility with certain recipients is improved, but availability is limited and not universally compatible with all recipients
Solution Approach 1:
The patent achieves universality by creating cell lines with inactivated ABO, RHD, and FUT1 genes, which eliminates the major histo-blood group antigens (A, B, H, and Rh(D)). This universal modification allows a single cell line to be compatible with all recipients regardless of their native blood type, transforming specialized blood-type-specific cells into universally compatible therapeutic cells
Solution Approach 2:
The patent changes the genetic parameters of cell lines by inactivating key genes (ABO, RHD, FUT1) that determine histo-blood type specificity. This parameter change transforms cells from being type-specific to being universally compatible, dramatically increasing the availability and adaptability of cell lines for therapeutic applications across all patient populations
Data Source
AI summary
Provided herein are cells with a gene modification of an ABO gene, RHD gene, and/or FUT1 gene. In some embodiments, the cells express reduced levels of a MHC I antigen and/or a MHC II antigen. In some instances, the cells are also hypoimmunogenic cells.