1/ Looking at Hypoimmune from $SANA
This is from the 10K and not my original work.
This is from the 10K and not my original work.
2/ Designing Hypoimmune Cells
Our goal is to create a universal cell that is able to evade immune detection, regardless of cell type or transplant location.
Our goal is to create a universal cell that is able to evade immune detection, regardless of cell type or transplant location.
3/ Our first-generation
technology, which is progressing through late-stage animal confirmatory studies, combines the three gene modifications below to hide these cells from
the host immune system:
technology, which is progressing through late-stage animal confirmatory studies, combines the three gene modifications below to hide these cells from
the host immune system:
4/ • disruption of MHC class I expression;
• disruption of MHC class II expression; and
• overexpression of CD47, a protein that hides cells from the innate immune system, including macrophages and NK cells.
• disruption of MHC class II expression; and
• overexpression of CD47, a protein that hides cells from the innate immune system, including macrophages and NK cells.
5/ First, the foregoing three edits were replicated in human iPSCs to engineer a human hypoimmune cell line that had comparable properties to the
mouse hypoimmune cells in vitro. Next, non-edited human iPSCs were transplanted into MHC mismatched humanized mice.
mouse hypoimmune cells in vitro. Next, non-edited human iPSCs were transplanted into MHC mismatched humanized mice.
6/ It was observed that these
non-edited human iPSCs were rapidly rejected. Human hypoimmune cells were then transplanted into MHC mismatched humanized mice.
non-edited human iPSCs were rapidly rejected. Human hypoimmune cells were then transplanted into MHC mismatched humanized mice.
7/ It was
observed that the human hypoimmune cells survived the full length of the experiment and failed to elicit any type of immune response. From this, it was
concluded that, in humanized mice, the human hypoimmune cells can evade the immune system.
observed that the human hypoimmune cells survived the full length of the experiment and failed to elicit any type of immune response. From this, it was
concluded that, in humanized mice, the human hypoimmune cells can evade the immune system.
8/ Pluripotency of human hypoimmune cells was
confirmed by differentiation into two different cell types, endothelial cells and cardiomyocytes. These differentiated cells exhibited the characteristics of
normal endothelial cells and cardiomyocytes.
confirmed by differentiation into two different cell types, endothelial cells and cardiomyocytes. These differentiated cells exhibited the characteristics of
normal endothelial cells and cardiomyocytes.
9/ Finally, to test whether these the differentiated cell types derived from human hypoimmune cells continue
to evade the immune system, the differentiated cells were transplanted into humanized mice, and the transplanted cells survived for the full standard
observation period.
to evade the immune system, the differentiated cells were transplanted into humanized mice, and the transplanted cells survived for the full standard
observation period.
10/ In contrast, differentiated cells derived from non-edited human iPSC cells did not survive after being transplanted, as anticipated.
11/ It
was also observed that the hypoimmune endothelial cells formed primitive vasculature with active blood flow and the hypoimmune cardiomyocyte cells
matured into functional-looking heart cells.
was also observed that the hypoimmune endothelial cells formed primitive vasculature with active blood flow and the hypoimmune cardiomyocyte cells
matured into functional-looking heart cells.
12/ They had NHP data since this time which I will have to try and find.
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