Methods of using ZSCAN4 for rejuvenating human cells
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Publication Number
US-11389504-B2
Publication Date
2022-07-19
Expiration Date
Abstract
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.
Core Innovation
The disclosure addresses treating a disease or condition with a karyotype abnormality by using Zscan4. Human bone marrow or blood cells are contacted with an isolated nucleic acid molecule encoding Zscan4 or with a Zscan4 protein, and the isolated nucleic acid molecule or the Zscan4 protein induces correction of the karyotype abnormality in the contacted cells. The karyotype abnormality is selected from chromosome trisomy and specific aneuploidies, and the disease or condition with the karyotype abnormality includes bone marrow failure.
The disclosure further provides an in vitro method of correcting a karyotype abnormality in one or more human non-embryonic cells by contacting the cells with an isolated nucleic acid molecule encoding Zscan4. The contacting is carried out such that the isolated nucleic acid molecule encoding Zscan4 induces correction of the karyotype abnormality in the one or more human non-embryonic cells, where the karyotype abnormality is selected from chromosome trisomy and specific aneuploidies. The disclosure encompasses nucleic-acid delivery formats that include vectors, and it also encompasses synthetic mRNA encoding Zscan4 in certain embodiments.
The disclosure states that Zscan4 biology and Zscan4 biologics include changes in marker gene expression and effects on telomere length and genome stability, together with therapeutic concepts for telomere and chromosome abnormalities. The described therapeutic concepts include correcting karyotype abnormalities and addressing conditions associated with aneuploidy and karyotype defects, including examples directed to bone marrow failure and disorders with telomere dysfunction. The disclosure also describes reported biological outcomes such as induced Zscan4 marker gene expression, telomere elongation, improved genome stability, effects on proliferation, and enhanced DNA repair capacity in the contexts described.
Claims Coverage
The partial content includes two independent claims: clm-00001 and clm-00011. Both claims focus on inducing correction of specified karyotype abnormalities in human cells using Zscan4 provided as an isolated nucleic acid molecule encoding Zscan4 or as a Zscan4 protein, with claim 1 limited to bone marrow failure in human bone marrow or blood cells and claim 11 directed to correction in human non-embryonic cells.
Zscan4-induced correction of karyotype abnormality for bone marrow failure
An in vitro method of treating a disease or condition with a karyotype abnormality by contacting one or more human bone marrow or blood cells isolated from a subject suffering from the disease or condition with the karyotype abnormality with an isolated nucleic acid molecule encoding Zscan4 or a Zscan4 protein, wherein the isolated nucleic acid molecule encoding Zscan4 or the Zscan4 protein induces correction of the karyotype abnormality in the one or more human bone marrow or blood cells, and wherein the karyotype abnormality is selected from chromosome trisomy and specific aneuploidies, and the disease or condition is bone marrow failure.
Zscan4-encoding nucleic acid for in vitro correction of karyotype abnormalities in non-embryonic cells
An in vitro method of correcting a karyotype abnormality in one or more human non-embryonic cells by contacting one or more human non-embryonic cells with an isolated nucleic acid molecule encoding Zscan4, wherein the one or more human non-embryonic cells have the karyotype abnormality, and wherein the isolated nucleic acid molecule encoding Zscan4 induces correction of the karyotype abnormality in the one or more human non-embryonic cells, wherein the karyotype abnormality is selected from chromosome trisomy and specific aneuploidies.
Across the two independent claims, the inventive focus is on using Zscan4 (as an isolated nucleic acid encoding Zscan4 and/or as a Zscan4 protein) to induce correction of specified karyotype abnormalities in human cells, with clm-00001 expressly tied to bone marrow failure in human bone marrow or blood cells and clm-00011 directed to correction in human non-embryonic cells.
Stated Advantages
Induces correction of the karyotype abnormality in the contacted human bone marrow or blood cells or human non-embryonic cells.
Provides therapeutic concepts for treating bone marrow failure associated with karyotype abnormalities.
Rapidly increases telomere length.
Improves genome stability and DNA repair capacity.
Corrects chromosome/karyotype abnormalities.
Corrects trisomy 21 in Down syndrome fibroblasts, with approximately 55% correction reported.
Documented Applications
In vitro treatment of a disease or condition with a karyotype abnormality, including bone marrow failure, by contacting human bone marrow or blood cells with Zscan4 nucleic acid or Zscan4 protein.
In vitro correction of karyotype abnormalities in one or more human non-embryonic cells by contacting the cells with an isolated nucleic acid molecule encoding Zscan4.
Treatment and therapeutic concepts for telomere/chromosome abnormalities and disorders associated with telomere and karyotype defects, as described in the disclosure (including examples involving telomere elongation, genome stability, and marker gene changes).
Treating diseases or conditions involving telomere shortening diseases using ZSCAN4/Zscan4 upregulation.
Treating bone marrow failure associated with karyotype abnormalities in human bone marrow or blood cells, including specified trisomies and aneuploidies.
Correcting karyotype abnormalities in human non-embryonic cells using an isolated nucleic acid molecule encoding Zscan4.
Correcting chromosome/karyotype abnormalities including trisomy 21 in Down syndrome fibroblasts.
Correcting chromosome/karyotype abnormalities in the context of Fanconi anemia telomere shortening.
Applications include treatment/rejuvenation use cases described as covering bone marrow failure syndromes, premature aging, and IVF/oocyte and embryo aneuploidy correction.
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