Elixirgen LLC

Baltimore, MD, United States

Elixirgen LLC

Baltimore, MD, United States
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Teratani-Ota Y.,U.S. National Institute on Aging | Teratani-Ota Y.,University of California at Davis | Yamamizu K.,U.S. National Institute on Aging | Yamamizu K.,Kyoto University | And 9 more authors.
In Vitro Cellular and Developmental Biology - Animal | Year: 2016

Summary: Specific neuronal types derived from embryonic stem cells (ESCs) can facilitate mechanistic studies and potentially aid in regenerative medicine. Existing induction methods, however, mostly rely on the effects of the combined action of multiple added growth factors, which generally tend to result in mixed populations of neurons. Here, we report that overexpression of specific transcription factors (TFs) in ESCs can rather guide the differentiation of ESCs towards specific neuron lineages. Analysis of data on gene expression changes 2 d after induction of each of 185 TFs implicated candidate TFs for further ESC differentiation studies. Induction of 23 TFs (out of 49 TFs tested) for 6 d facilitated neural differentiation of ESCs as inferred from increased proportion of cells with neural progenitor marker PSA-NCAM. We identified early activation of the Notch signaling pathway as a common feature of most potent inducers of neural differentiation. The majority of neuron-like cells generated by induction of Ascl1, Smad7, Nr2f1, Dlx2, Dlx4, Nr2f2, Barhl2, and Lhx1 were GABA-positive and expressed other markers of GABAergic neurons. In the same way, we identified Lmx1a and Nr4a2 as inducers for neurons bearing dopaminergic markers and Isl1, Fezf2, and St18 for cholinergic motor neurons. A time-course experiment with induction of Ascl1 showed early upregulation of most neural-specific messenger RNA (mRNA) and microRNAs (miRNAs). Sets of Ascl1-induced mRNAs and miRNAs were enriched in Ascl1 targets. In further studies, enrichment of cells obtained with the induction of Ascl1, Smad7, and Nr2f1 using microbeads resulted in essentially pure population of neuron-like cells with expression profiles similar to neural tissues and expressed markers of GABAergic neurons. In summary, this study indicates that induction of transcription factors is a promising approach to generate cultures that show the transcription profiles characteristic of specific neural cell types. © 2016 The Society for In Vitro Biology


Amano T.,Elixirgen LLC | Jeffries E.,Elixirgen LLC | Amano M.,Elixirgen LLC | Ko A.C.,Elixirgen LLC | And 3 more authors.
DNA Research | Year: 2015

Aneuploidy, an abnormal number of chromosomes, has previously been considered irremediable. Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in stem cells. For footprint-free delivery of ZSCAN4 to cells, we developed ZSCAN4 synthetic mRNAs and Sendai virus vectors that encode human ZSCAN4. Applying the ZSCAN4 biologics to established cultures of mouse embryonic stem cells, most of which had become aneuploid and polyploid, dramatically increased the number of euploid cells within a few days. We then tested the biologics on non-immortalized primary human fibroblast cells derived from four individuals with Down syndrome-the most frequent autosomal trisomy of chromosome 21. Within weeks after ZSCAN4 application to the cells in culture, fluorescent in situ hybridization with a chromosome 21-specific probe detected the emergence of up to 24% of cells with only two rather than three copies. High-resolution G-banded chromosomes further showed up to 40% of cells with a normal karyotype. These findings were confirmed by whole-exome sequencing. Similar results were obtained for cells with the trisomy 18 of Edwards syndrome. Thus a direct, efficient correction of aneuploidy in human fibroblast cells seems possible in vitro using human ZSCAN4. © 2015 The Author.


Patent
Elixirgen LLC | Date: 2014-03-14

The present disclosure relates to methods for increasing telomere length in one or more human adult cells and/or increasing genome stability of one or more human adult cells, for example by contacting one or more human adult cells with an agent that increases expression of Zscan4 in the one or more human adult cells. Methods of treating a subject in need of telomere lengthening, treating a disease or condition associated with a telomere abnormality, of rejuvenating one or more human adult cells, of rejuvenating tissues or organs, and of rejuvenating a subject in need thereof, for example by contacting one or more human adult 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 is also provided.


Patent
Elixirgen Llc | Date: 2014-03-14

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.


Grant
Agency: Department of Health and Human Services | Branch: National Institutes of Health | Program: SBIR | Phase: Phase I | Award Amount: 148.40K | Year: 2016

Program Director Principal Investigator Last First Middle Ko Minoru S H Dyskeratosis congenita DKC is a rare genetic disease that occurs at the rate of in million births and caused by mutations in genes involved in the regulation of telomere lengths Although there are multiple gene mutations causing DKC all the patients carry significantly shorter telomeres and eventually develop bone marrow failure which is the main cause of premature mortality in DKC patients There has been no effective treatment for DKC patients Here we would like to propose the product of human ZSCAN gene as a biologic to treat DKC patients We have originally identified mouse Zscan a novel protein expressed specifically in cell stage mouse embryos and have published a number of unusual features of Zscan functions in mouse ES cells i to rapidly extend telomeres by homologous recombination called alternative lengthening of telomeres which is independent of telomerase ii to increase genome stability and maintain normal karyotype by transient and occasional expression iii to increase developmental potential iv to block de novo synthesis of proteins transiently v to increase the efficiency and quality of induced pluripotent stem iPS cells when used as one of the reprogramming factors and vi to function as a potent epigenetic modifier and transiently open chromatin Based on these functions of mouse Zscan we hypothesize that transient overexpression of human ZSCAN protein extends telomeres in bone marrow cells from DKC patients by homologous recombination based mechanisms and eventually alleviates bone marrow failure in DKC patients In this SBIR Phase I proposal we would like to demonstrate that transient overexpression of ZSCAN elongates telomeres in fibroblast cells derived from DKC patients We would also like to demonstrate that ZSCAN biologics can be delivered to bone marrow using a mouse model The proposed project if successful will offer a first step towards a dramatically new therapy for patients with DKC In addition the biologicandapos s mechanisms are very much applicable to other related bone marrow and telomere related disorders such as myelodysplastic syndrome and Fanconi anemia OMB No Rev Approved Through Page Continuation Format PageProgram Director Principal Investigator Last First Middle Ko Minoru S H Narrative A novel medical product will be developed to treat bone marrow failure in patients with dyskeratosis congenita and other diseases OMB No Rev Approved Through Page Continuation Format Page


PubMed | Elixirgen LLC and Keio University
Type: Journal Article | Journal: DNA research : an international journal for rapid publication of reports on genes and genomes | Year: 2015

Aneuploidy, an abnormal number of chromosomes, has previously been considered irremediable. Here, we report findings that euploid cells increased among cultured aneuploid cells after exposure to the protein ZSCAN4, encoded by a mammalian-specific gene that is ordinarily expressed in preimplantation embryos and occasionally in stem cells. For footprint-free delivery of ZSCAN4 to cells, we developed ZSCAN4 synthetic mRNAs and Sendai virus vectors that encode human ZSCAN4. Applying the ZSCAN4 biologics to established cultures of mouse embryonic stem cells, most of which had become aneuploid and polyploid, dramatically increased the number of euploid cells within a few days. We then tested the biologics on non-immortalized primary human fibroblast cells derived from four individuals with Down syndromethe most frequent autosomal trisomy of chromosome 21. Within weeks after ZSCAN4 application to the cells in culture, fluorescent in situ hybridization with a chromosome 21-specific probe detected the emergence of up to 24% of cells with only two rather than three copies. High-resolution G-banded chromosomes further showed up to 40% of cells with a normal karyotype. These findings were confirmed by whole-exome sequencing. Similar results were obtained for cells with the trisomy 18 of Edwards syndrome. Thus a direct, efficient correction of aneuploidy in human fibroblast cells seems possible in vitro using human ZSCAN4.


Trademark
Elixirgen LLC | Date: 2016-10-01

pharmaceutical preparations and substances; chemicals and chemical preparations for medical and pharmaceutical purposes. Development of pharmaceutical product; Test and examination or research and development of pharmaceutical product; Research and development of pharmaceutical products and medical products.


Trademark
Elixirgen LLC | Date: 2016-10-01

Chemical reagent for cell culturing (excluding medical and veterinary applications); Reagent for cell separation (excluding medical and veterinary applications); Reagent for detection or quantitative determination of cell or cytoplasm (excluding medical and veterinary applications); Test paper for determination of chemical properties of reagent; Chemical reagent for identification of type of DNA (excluding medical and veterinary applications); Reagent as kit for bacteria examination (excluding medical and veterinary applications); Blocking reagent for bioassay (excluding medical and veterinary applications); Stabilizing reagent for bioassay (excluding medical and veterinary applications); Chemical reagent for genetic research (excluding medical and veterinary applications); Reagent for genetic research (excluding medical and veterinary applications); Chemical reagent for use in detection and measurement and identification of genetic material or compound (excluding medical and veterinary applications); Chemical reagent for separation and production of genetically engineered substance; Reagent for sterility test of medical equipment; Chemical reagent as kit including chemical substance and biochemical substance (excluding medical and veterinary applications); Reagent for chemical analysis; Chemical reagent for analysis of nucleic acid (excluding medical and veterinary applications); Reagent for research (excluding medical and veterinary applications).


Trademark
Elixirgen LLC | Date: 2016-10-01

Chemical reagent for cell culturing (excluding medical and veterinary applications); Reagent for cell separation (excluding medical and veterinary applications); Reagent for detection or quantitative determination of cell or cytoplasm (excluding medical and veterinary applications); Test paper for determination of chemical properties of reagent; Chemical reagent for identification of type of DNA (excluding medical and veterinary applications); Reagent as kit for bacteria examination (excluding medical and veterinary applications); Blocking reagent for bioassay (excluding medical and veterinary applications); Stabilizing reagent for bioassay (excluding medical and veterinary applications); Chemical reagent for genetic research (excluding medical and veterinary applications); Reagent for genetic research (excluding medical and veterinary applications); Chemical reagent for use in detection and measurement and identification of genetic material or compound (excluding medical and veterinary applications); Chemical reagent for separation and production of genetically engineered substance; Reagent for sterility test of medical equipment; Chemical reagent as kit including chemical substance and biochemical substance (excluding medical and veterinary applications); Reagent for chemical analysis; Chemical reagent for analysis of nucleic acid (excluding medical and veterinary applications); Reagent for research (excluding medical and veterinary applications).


Trademark
Elixirgen LLC | Date: 2016-10-01

Chemical reagent for cell culturing (excluding medical and veterinary applications); Reagent for cell separation (excluding medical and veterinary applications); Reagent for detection or quantitative determination of cell or cytoplasm (excluding medical and veterinary applications); Test paper for determination of chemical properties of reagent; Chemical reagent for identification of type of DNA (excluding medical and veterinary applications); Reagent as kit for bacteria examination (excluding medical and veterinary applications); Blocking reagent for bioassay (excluding medical and veterinary applications); Stabilizing reagent for bioassay (excluding medical and veterinary applications); Chemical reagent for genetic research (excluding medical and veterinary applications); Reagent for genetic research (excluding medical and veterinary applications); Chemical reagent for use in detection and measurement and identification of genetic material or compound (excluding medical and veterinary applications); Chemical reagent for separation and production of genetically engineered substance; Reagent for sterility test of medical equipment; Chemical reagent as kit including chemical substance and biochemical substance (excluding medical and veterinary applications); Reagent for chemical analysis; Chemical reagent for analysis of nucleic acid (excluding medical and veterinary applications); Reagent for research (excluding medical and veterinary applications).

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