Correction of a Genetic Defect by Nuclear Transplantation and Combined Cell and Gene Therapy
Immune-deficient Rag2 −/− mice were used as nuclear donors for transfer into enucleated oocytes, and the resulting blastocysts were cultured to isolate an isogenic embryonic stem cell line. One of the mutated alleles in the Rag2 −/− ES cells was repaired by homologous recombination, thereby restorin...
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| Veröffentlicht in: | Cell 2002-04, Vol.109 (1), p.17-27 |
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| creator | Rideout, William M. Hochedlinger, Konrad Kyba, Michael Daley, George Q. Jaenisch, Rudolf |
| description | Immune-deficient Rag2
−/− mice were used as nuclear donors for transfer into enucleated oocytes, and the resulting blastocysts were cultured to isolate an isogenic embryonic stem cell line. One of the mutated alleles in the Rag2
−/− ES cells was repaired by homologous recombination, thereby restoring normal Rag2 gene structure. Mutant mice were treated with the repaired ES cells in two ways. (1) Immune-competent mice were generated from the repaired ES cells by tetraploid embryo complementation and were used as bone marrow donors for transplantation. (2) Hematopoietic precursors were derived by in vitro differentiation from the repaired ES cells and engrafted into mutant mice. Mature myeloid and lymphoid cells as well as immunoglobulins became detectable 3–4 weeks after transplantation. Our results establish a paradigm for the treatment of a genetic disorder by combining therapeutic cloning with gene therapy. |
| doi_str_mv | 10.1016/S0092-8674(02)00681-5 |
| format | Article |
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−/− ES cells was repaired by homologous recombination, thereby restoring normal Rag2 gene structure. Mutant mice were treated with the repaired ES cells in two ways. (1) Immune-competent mice were generated from the repaired ES cells by tetraploid embryo complementation and were used as bone marrow donors for transplantation. (2) Hematopoietic precursors were derived by in vitro differentiation from the repaired ES cells and engrafted into mutant mice. Mature myeloid and lymphoid cells as well as immunoglobulins became detectable 3–4 weeks after transplantation. Our results establish a paradigm for the treatment of a genetic disorder by combining therapeutic cloning with gene therapy.</description><identifier>ISSN: 0092-8674</identifier><identifier>EISSN: 1097-4172</identifier><identifier>DOI: 10.1016/S0092-8674(02)00681-5</identifier><identifier>PMID: 11955443</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Blastocyst - cytology ; Blastocyst - immunology ; Blastocyst - metabolism ; Bone Marrow Transplantation ; Cell Differentiation - genetics ; Cell Nucleus - genetics ; Cell Nucleus - immunology ; Cloning, Organism - methods ; Disease Models, Animal ; DNA-Binding Proteins - deficiency ; DNA-Binding Proteins - genetics ; Embryo Transfer ; Female ; Genetic Therapy ; Graft Survival - genetics ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells - cytology ; Hematopoietic Stem Cells - immunology ; Hematopoietic Stem Cells - metabolism ; Male ; Mice ; Mice, Knockout ; Mice, SCID ; Mutation - genetics ; Nuclear Transfer Techniques ; Oocytes - cytology ; Oocytes - immunology ; Oocytes - metabolism ; Polyploidy ; Severe Combined Immunodeficiency - genetics ; Severe Combined Immunodeficiency - immunology ; Severe Combined Immunodeficiency - therapy</subject><ispartof>Cell, 2002-04, Vol.109 (1), p.17-27</ispartof><rights>2002 Cell Press</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c505t-e198f374c1e9a0cbc2b4e3cc1e0868e0ac1d5002595849f613667e752a94f1e73</citedby><cites>FETCH-LOGICAL-c505t-e198f374c1e9a0cbc2b4e3cc1e0868e0ac1d5002595849f613667e752a94f1e73</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/S0092-8674(02)00681-5$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/11955443$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Rideout, William M.</creatorcontrib><creatorcontrib>Hochedlinger, Konrad</creatorcontrib><creatorcontrib>Kyba, Michael</creatorcontrib><creatorcontrib>Daley, George Q.</creatorcontrib><creatorcontrib>Jaenisch, Rudolf</creatorcontrib><title>Correction of a Genetic Defect by Nuclear Transplantation and Combined Cell and Gene Therapy</title><title>Cell</title><addtitle>Cell</addtitle><description>Immune-deficient Rag2
−/− mice were used as nuclear donors for transfer into enucleated oocytes, and the resulting blastocysts were cultured to isolate an isogenic embryonic stem cell line. One of the mutated alleles in the Rag2
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Our results establish a paradigm for the treatment of a genetic disorder by combining therapeutic cloning with gene therapy.</description><subject>Animals</subject><subject>Blastocyst - cytology</subject><subject>Blastocyst - immunology</subject><subject>Blastocyst - metabolism</subject><subject>Bone Marrow Transplantation</subject><subject>Cell Differentiation - genetics</subject><subject>Cell Nucleus - genetics</subject><subject>Cell Nucleus - immunology</subject><subject>Cloning, Organism - methods</subject><subject>Disease Models, Animal</subject><subject>DNA-Binding Proteins - deficiency</subject><subject>DNA-Binding Proteins - genetics</subject><subject>Embryo Transfer</subject><subject>Female</subject><subject>Genetic Therapy</subject><subject>Graft Survival - genetics</subject><subject>Hematopoietic Stem Cell Transplantation</subject><subject>Hematopoietic Stem Cells - cytology</subject><subject>Hematopoietic Stem Cells - immunology</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Mice, SCID</subject><subject>Mutation - genetics</subject><subject>Nuclear Transfer Techniques</subject><subject>Oocytes - cytology</subject><subject>Oocytes - immunology</subject><subject>Oocytes - metabolism</subject><subject>Polyploidy</subject><subject>Severe Combined Immunodeficiency - genetics</subject><subject>Severe Combined Immunodeficiency - immunology</subject><subject>Severe Combined Immunodeficiency - therapy</subject><issn>0092-8674</issn><issn>1097-4172</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2002</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcFKxDAQhoMo7rr6CEpOoofqpG3a5CRSdRUWPbjehJCmU4x02zVphX172-6iR09Jhu-fGb4QcsrgigFLrl8BZBiIJI0vILwESAQL-B6ZMpBpELM03CfTX2RCjrz_BADBOT8kE8Yk53EcTcl71jiHprVNTZuSajrHGltr6B2WfZnmG_rcmQq1o0una7-udN3qEdd1QbNmldsa-wtW1VgZ8nT5gU6vN8fkoNSVx5PdOSNvD_fL7DFYvMyfsttFYDjwNkAmRRmlsWEoNZjchHmMkemfIBKBoA0rOEDIJRexLBMWJUmKKQ-1jEuGaTQj59u-a9d8dehbtbLe9BvpGpvOq5QlEAou_wWZiGQvaejIt6BxjfcOS7V2dqXdRjFQg381-leDXAWhGv0r3ufOdgO6fIXFX2onvAdutgD2Pr4tOuWNxdpgYYdvUEVj_xnxA5P4k7U</recordid><startdate>20020405</startdate><enddate>20020405</enddate><creator>Rideout, William M.</creator><creator>Hochedlinger, Konrad</creator><creator>Kyba, Michael</creator><creator>Daley, George Q.</creator><creator>Jaenisch, Rudolf</creator><general>Elsevier Inc</general><scope>6I.</scope><scope>AAFTH</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>20020405</creationdate><title>Correction of a Genetic Defect by Nuclear Transplantation and Combined Cell and Gene Therapy</title><author>Rideout, William M. ; Hochedlinger, Konrad ; Kyba, Michael ; Daley, George Q. ; Jaenisch, Rudolf</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c505t-e198f374c1e9a0cbc2b4e3cc1e0868e0ac1d5002595849f613667e752a94f1e73</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2002</creationdate><topic>Animals</topic><topic>Blastocyst - cytology</topic><topic>Blastocyst - immunology</topic><topic>Blastocyst - metabolism</topic><topic>Bone Marrow Transplantation</topic><topic>Cell Differentiation - genetics</topic><topic>Cell Nucleus - genetics</topic><topic>Cell Nucleus - immunology</topic><topic>Cloning, Organism - methods</topic><topic>Disease Models, Animal</topic><topic>DNA-Binding Proteins - deficiency</topic><topic>DNA-Binding Proteins - genetics</topic><topic>Embryo Transfer</topic><topic>Female</topic><topic>Genetic Therapy</topic><topic>Graft Survival - genetics</topic><topic>Hematopoietic Stem Cell Transplantation</topic><topic>Hematopoietic Stem Cells - cytology</topic><topic>Hematopoietic Stem Cells - immunology</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Knockout</topic><topic>Mice, SCID</topic><topic>Mutation - genetics</topic><topic>Nuclear Transfer Techniques</topic><topic>Oocytes - cytology</topic><topic>Oocytes - immunology</topic><topic>Oocytes - metabolism</topic><topic>Polyploidy</topic><topic>Severe Combined Immunodeficiency - genetics</topic><topic>Severe Combined Immunodeficiency - immunology</topic><topic>Severe Combined Immunodeficiency - therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Rideout, William M.</creatorcontrib><creatorcontrib>Hochedlinger, Konrad</creatorcontrib><creatorcontrib>Kyba, Michael</creatorcontrib><creatorcontrib>Daley, George Q.</creatorcontrib><creatorcontrib>Jaenisch, Rudolf</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cell</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Rideout, William M.</au><au>Hochedlinger, Konrad</au><au>Kyba, Michael</au><au>Daley, George Q.</au><au>Jaenisch, Rudolf</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Correction of a Genetic Defect by Nuclear Transplantation and Combined Cell and Gene Therapy</atitle><jtitle>Cell</jtitle><addtitle>Cell</addtitle><date>2002-04-05</date><risdate>2002</risdate><volume>109</volume><issue>1</issue><spage>17</spage><epage>27</epage><pages>17-27</pages><issn>0092-8674</issn><eissn>1097-4172</eissn><abstract>Immune-deficient Rag2
−/− mice were used as nuclear donors for transfer into enucleated oocytes, and the resulting blastocysts were cultured to isolate an isogenic embryonic stem cell line. One of the mutated alleles in the Rag2
−/− ES cells was repaired by homologous recombination, thereby restoring normal Rag2 gene structure. Mutant mice were treated with the repaired ES cells in two ways. (1) Immune-competent mice were generated from the repaired ES cells by tetraploid embryo complementation and were used as bone marrow donors for transplantation. (2) Hematopoietic precursors were derived by in vitro differentiation from the repaired ES cells and engrafted into mutant mice. Mature myeloid and lymphoid cells as well as immunoglobulins became detectable 3–4 weeks after transplantation. Our results establish a paradigm for the treatment of a genetic disorder by combining therapeutic cloning with gene therapy.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>11955443</pmid><doi>10.1016/S0092-8674(02)00681-5</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Cell Press Free Archives; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; ScienceDirect Journals (5 years ago - present) |
| subjects | Animals Blastocyst - cytology Blastocyst - immunology Blastocyst - metabolism Bone Marrow Transplantation Cell Differentiation - genetics Cell Nucleus - genetics Cell Nucleus - immunology Cloning, Organism - methods Disease Models, Animal DNA-Binding Proteins - deficiency DNA-Binding Proteins - genetics Embryo Transfer Female Genetic Therapy Graft Survival - genetics Hematopoietic Stem Cell Transplantation Hematopoietic Stem Cells - cytology Hematopoietic Stem Cells - immunology Hematopoietic Stem Cells - metabolism Male Mice Mice, Knockout Mice, SCID Mutation - genetics Nuclear Transfer Techniques Oocytes - cytology Oocytes - immunology Oocytes - metabolism Polyploidy Severe Combined Immunodeficiency - genetics Severe Combined Immunodeficiency - immunology Severe Combined Immunodeficiency - therapy |
| title | Correction of a Genetic Defect by Nuclear Transplantation and Combined Cell and Gene Therapy |
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