Modulating TLR/NF-KB and P53 signaling pathways to enhance interspecies chimerism between evolutionaryily distant species
AssigneeBoard of Regents, The University of Texas System
InventorsJun Wu, Canbin Zheng, Yingying Hu
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Abstract
Disclosed herein are chimeric blastocysts, such as chimeric blastocysts derived from a host blastocyst from a first mammalian species and having donor pluripotent stem cells from a second mammalian species, wherein the donor pluripotent stem cells have reduced expression or reduced biological activity of one or more proteins in the TLR/NF-kB signaling pathway or the p53 pathway. Methods of preparing chimeric blastocysts and methods of obtaining mammalian organs and tissues are also provided.
Claims4
A chimeric blastocyst, comprising:
- (i) a host blastocyst from a first mammalian species, wherein the host blastocyst is an organogenesis disabled blastocyst comprising a genetic deficiency and wherein the first mammalian species is a rodent;
- and
- (ii) donor pluripotent stem cells from a second mammalian species,
- wherein the donor pluripotent stem cells have a homozygous disruption of one or more of p65 and MYD88, wherein said homozygous disruption leads to reduced expression or reduced biological activity of one or more of p65 and MYD88, and
- wherein the second mammalian species is a human.
A method of preparing a chimeric blastocyst comprising:
- injecting a host blastocyst from a first mammalian species, wherein the first mammalian species is a rodent, with donor pluripotent stem cells from a second mammalian species, wherein the second mammalian species is a human,
- wherein the host blastocyst is an organogenesis disabled blastocyst comprising a genetic deficiency,
- wherein the donor pluripotent stem cells have a homozygous disruption of one or more of p65 and MYD88, wherein said homozygous disruption leads to reduced expression or reduced biological activity of one or more of p65 and MYD88.
Dependencies are inferred from the claim text.