Immune rejection of transplanted stem cells and their differentiated derivatives is mediated by the polymorphic human leukocyte antigen (HLA) proteins.
We solve the problem of immune rejection by the complete genetic engineering of HLA expression.
Universal Cells uses a proprietary genetic engineering technique to completely control HLA expression and create non-immunogenic cells for therapeutic applications.
Our patented technology is based on recombinant adeno-associated virus (rAAV)-mediated gene editing, which offers high accuracy and safety, and the best vehicle available for cellular delivery. Stem cells are targeted with our patented stem cell-tropic AAV3b serotype.
Recombinant adeno-associated virus (rAAV) vectors are single-stranded DNA vectors that efficiently infect stem cells and edit the genome by homologous recombination. The rAAV genome (green) is engineered to contain DNA sequences homologous to a chromosomal target gene (blue arrows). The rAAV sequence can include mutations to knockout gene expression or knock-in new genes of interest (red). The diagram displays the introduction of a disrupting mutation into the Beta-2-Microglobulin gene (B2M).
Universal Cells' technology enables the complete engineering of HLA class I and class II expression. We eliminate the expression of all polymorphic HLA proteins, and reintroduce only the specific HLA molecules required for a given indication.
For example, we can remove all HLA class I molecules from the cell surface and simultaneously re-introduce a non-polymorphic HLA-E molecule to prevent lysis by Natural Killer cells. Customized HLA molecules can also be expressed in order to present specific peptides.
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Genetic engineering of HLA class I
Parent cells express 6 polymorphic HLA class I molecules (HLA-A, B & C) that need to be matched to each transplant recipient (colored circles).
Both alleles of B2M are knocked out by gene editing with rAAV to prevent HLA-A, B & C expression, while a single-chain, non-polymorphic HLA-E molecule (gray circles) is simultaneously reintroduced by knock-in at one B2M allele.