METHODS OF USING ZSCAN4 FOR REJUVENATING HUMAN CELLS
The present disclosure relates to methods for increasing telomere length in one or more human cells and/or increasing genome stability of one or more human cells, for example by contacting one or more human cells with an agent that increases expression of Zscan4 in the one or more human cells. Methods of treating a subject in need of telomere lengthening, treating a disease or condition associated with a genomic and/or chromosome abnormality, of rejuvenating one or more human cells, of rejuvenating tissues or organs, and of rejuvenating a subject in need thereof, for example by contacting one or more human cells in the subject with an agent that increases expression of Zscan4, or by administering to a subject in need thereof, an agent that increases expression of Zscan4 are also provided.
1 - 104 . (canceled)
105 . A method of treating a disease or condition with a chromosome abnormality, comprising:
i. contacting one or more human bone marrow or blood cells with an isolated nucleic acid molecule encoding Zscan4 or a Zscan4 protein, and wherein the isolated nucleic acid molecule encoding Zscan4 or the Zscan4 protein induces extension of telomeres in the one or more human bone marrow or blood cells; and
ii. engrafting the contacted one or more human bone marrow or blood cells into the subject to treat the disease or condition with the chromosome abnormality, wherein the chromosomal abnormality is telomere shortening, and wherein the disease or condition with the chromosomal abnormality is a bone marrow failure.
106 . The method of claim 105 , wherein the one or more human cells are isolated from the subject suffering from the disease or condition associated with the chromosome abnormality.
107 . The method of claim 105 , wherein the disease or condition is selected from the group consisting of dyskeratosis congenita, Hoyeraal-Hreidarsson syndrome, Revesz syndrome, Coats plus syndrome, idiopathic pulmonary fibrosis, liver cirrhosis, pancreatic fibrosis, Fanconi anemia, amegakaryocytic thrombocytopenia, aplastic anemia, Diamond Blackfan anemia, paroxysmal nocturnal hemoglobinuria (PNH), Pearson syndrome, Shwachman Diamond syndrome, thrombocytopenia, myelodysplastic syndrome Cockayne syndrome, Xeroderma pigmentosa, Ataxia telangiectasia, and Rothmund Thomson syndrome.
108 . The method of claim 105 , wherein the one or more human bone marrow or blood cells are mesenchymal stem cells, CD34 + cells, hematopoietic stem cells, hematopoietic progenitor cells, endothelial progenitor cells, or any combinations thereof.
109 . The method of claim 105 , wherein the one or more human bone marrow or blood cells are contacted with the isolated nucleic acid molecule encoding Zscan4.
110 . The method of claim 109 , wherein the isolated nucleic acid molecule is a synthetic mRNA.
111 . The method of claim 109 , wherein the isolated nucleic acid molecule is comprised in a vector.
112 . The method of claim 111 , wherein the vector is a Sendai virus vector.
113 . The method of claim 109 , wherein the Zscan4 is a Zscan4-ERT2 fusion protein or a Zscan4-ΔC protein.
114 . The method of claim 109 , wherein the Zscan4 is mouse Zscan4, human ZSCAN4, or a homolog thereof.
115 . The method of claim 105 , wherein the one or more human bone marrow or blood cells are contacted with the Zscan4 protein.
116 . The method of claim 115 , wherein the Zscan4 protein is fused to a cell-penetrating peptide.
117 . The method of claim 115 , wherein the Zscan4 protein is a mouse Zscan4 protein, a human ZSCAN4 protein, or a homolog thereof.
118 . The method of claim 115 , wherein the Zscan4 protein is a Zscan4-ERT2 fusion protein or a Zscan4-ΔC protein.
119 . The method of claim 105 , wherein the blood cells are peripheral blood cells.