Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo
Holt et al . describe an anti-HIV strategy in which human hematopoietic stem/progenitor cells are modified with zinc-finger nucleases to knock out the viral co-receptor CCR5. Transplantation of these cells into mice confers resistance to HIV, as shown by higher human T-cell counts and lower viral lo...
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| Veröffentlicht in: | Nature biotechnology 2010-08, Vol.28 (8), p.839-847 |
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| creator | Holt, Nathalia Wang, Jianbin Kim, Kenneth Friedman, Geoffrey Wang, Xingchao Taupin, Vanessa Crooks, Gay M Kohn, Donald B Gregory, Philip D Holmes, Michael C Cannon, Paula M |
| description | Holt
et al
. describe an anti-HIV strategy in which human hematopoietic stem/progenitor cells are modified with zinc-finger nucleases to knock out the viral co-receptor CCR5. Transplantation of these cells into mice confers resistance to HIV, as shown by higher human T-cell counts and lower viral loads compared with animals that received unmodified cells.
CCR5 is the major HIV-1 co-receptor, and individuals homozygous for a 32-bp deletion in
CCR5
are resistant to infection by CCR5-tropic HIV-1. Using engineered zinc-finger nucleases (ZFNs), we disrupted
CCR5
in human CD34
+
hematopoietic stem/progenitor cells (HSPCs) at a mean frequency of 17% of the total alleles in a population. This procedure produces both mono- and bi-allelically disrupted cells. ZFN-treated HSPCs retained the ability to engraft NOD/SCID/IL2rγ
null
mice and gave rise to polyclonal multi-lineage progeny in which
CCR5
was permanently disrupted. Control mice receiving untreated HSPCs and challenged with CCR5-tropic HIV-1 showed profound CD4
+
T-cell loss. In contrast, mice transplanted with ZFN-modified HSPCs underwent rapid selection for
CCR5
−/−
cells, had significantly lower HIV-1 levels and preserved human cells throughout their tissues. The demonstration that a minority of
CCR5
−/−
HSPCs can populate an infected animal with HIV-1-resistant,
CCR5
−/−
progeny supports the use of ZFN-modified autologous hematopoietic stem cells as a clinical approach to treating HIV-1. |
| doi_str_mv | 10.1038/nbt.1663 |
| format | Article |
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et al
. describe an anti-HIV strategy in which human hematopoietic stem/progenitor cells are modified with zinc-finger nucleases to knock out the viral co-receptor CCR5. Transplantation of these cells into mice confers resistance to HIV, as shown by higher human T-cell counts and lower viral loads compared with animals that received unmodified cells.
CCR5 is the major HIV-1 co-receptor, and individuals homozygous for a 32-bp deletion in
CCR5
are resistant to infection by CCR5-tropic HIV-1. Using engineered zinc-finger nucleases (ZFNs), we disrupted
CCR5
in human CD34
+
hematopoietic stem/progenitor cells (HSPCs) at a mean frequency of 17% of the total alleles in a population. This procedure produces both mono- and bi-allelically disrupted cells. ZFN-treated HSPCs retained the ability to engraft NOD/SCID/IL2rγ
null
mice and gave rise to polyclonal multi-lineage progeny in which
CCR5
was permanently disrupted. Control mice receiving untreated HSPCs and challenged with CCR5-tropic HIV-1 showed profound CD4
+
T-cell loss. In contrast, mice transplanted with ZFN-modified HSPCs underwent rapid selection for
CCR5
−/−
cells, had significantly lower HIV-1 levels and preserved human cells throughout their tissues. The demonstration that a minority of
CCR5
−/−
HSPCs can populate an infected animal with HIV-1-resistant,
CCR5
−/−
progeny supports the use of ZFN-modified autologous hematopoietic stem cells as a clinical approach to treating HIV-1.</description><identifier>ISSN: 1087-0156</identifier><identifier>EISSN: 1546-1696</identifier><identifier>DOI: 10.1038/nbt.1663</identifier><identifier>PMID: 20601939</identifier><identifier>CODEN: NABIF9</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/532/1542 ; 631/61/51/2315 ; 692/699/249/1570/1901 ; Agriculture ; AIDS treatment ; Alleles ; Animals ; Autografts ; B cells ; Bioinformatics ; Biological and medical sciences ; Biomedical Engineering/Biotechnology ; Biomedicine ; Biotechnology ; Cells (Biology) ; Cellular biology ; Comparative analysis ; Control ; Development and progression ; DNA binding proteins ; Endonucleases - genetics ; Endonucleases - metabolism ; Fundamental and applied biological sciences. Psychology ; Gene Deletion ; Gene expression ; Gene therapy ; Genetic aspects ; Genetic Engineering - methods ; Health aspects ; Health. Pharmaceutical industry ; Hematopoietic Stem Cell Transplantation - methods ; Hematopoietic stem cells ; Hematopoietic Stem Cells - metabolism ; HIV ; HIV infection ; HIV Infections - immunology ; HIV Infections - therapy ; HIV Infections - virology ; HIV-1 - immunology ; HIV-1 - metabolism ; Human immunodeficiency virus ; Human immunodeficiency virus 1 ; Humans ; Industrial applications and implications. Economical aspects ; Infection ; Life Sciences ; Medical schools ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Miscellaneous ; Nucleases ; Physiological aspects ; Properties ; Receptors, CCR5 - genetics ; Receptors, CCR5 - metabolism ; Rodents ; Stem cells ; Stem Cells - metabolism ; Surgery ; T cells ; T-Lymphocytes - immunology ; T-Lymphocytes - metabolism ; Zinc ; Zinc finger proteins ; Zinc Fingers - genetics ; Zinc Fingers - physiology</subject><ispartof>Nature biotechnology, 2010-08, Vol.28 (8), p.839-847</ispartof><rights>Springer Nature Limited 2010</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2010 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2010</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c810t-48af9f181dad38c117ecf4e74c5b45e348ad3fb42e1023d363097ceb4d30e2ce3</citedby><cites>FETCH-LOGICAL-c810t-48af9f181dad38c117ecf4e74c5b45e348ad3fb42e1023d363097ceb4d30e2ce3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1038/nbt.1663$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nbt.1663$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,777,781,27905,27906,41469,42538,51300</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23147047$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20601939$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Holt, Nathalia</creatorcontrib><creatorcontrib>Wang, Jianbin</creatorcontrib><creatorcontrib>Kim, Kenneth</creatorcontrib><creatorcontrib>Friedman, Geoffrey</creatorcontrib><creatorcontrib>Wang, Xingchao</creatorcontrib><creatorcontrib>Taupin, Vanessa</creatorcontrib><creatorcontrib>Crooks, Gay M</creatorcontrib><creatorcontrib>Kohn, Donald B</creatorcontrib><creatorcontrib>Gregory, Philip D</creatorcontrib><creatorcontrib>Holmes, Michael C</creatorcontrib><creatorcontrib>Cannon, Paula M</creatorcontrib><title>Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo</title><title>Nature biotechnology</title><addtitle>Nat Biotechnol</addtitle><addtitle>Nat Biotechnol</addtitle><description>Holt
et al
. describe an anti-HIV strategy in which human hematopoietic stem/progenitor cells are modified with zinc-finger nucleases to knock out the viral co-receptor CCR5. Transplantation of these cells into mice confers resistance to HIV, as shown by higher human T-cell counts and lower viral loads compared with animals that received unmodified cells.
CCR5 is the major HIV-1 co-receptor, and individuals homozygous for a 32-bp deletion in
CCR5
are resistant to infection by CCR5-tropic HIV-1. Using engineered zinc-finger nucleases (ZFNs), we disrupted
CCR5
in human CD34
+
hematopoietic stem/progenitor cells (HSPCs) at a mean frequency of 17% of the total alleles in a population. This procedure produces both mono- and bi-allelically disrupted cells. ZFN-treated HSPCs retained the ability to engraft NOD/SCID/IL2rγ
null
mice and gave rise to polyclonal multi-lineage progeny in which
CCR5
was permanently disrupted. Control mice receiving untreated HSPCs and challenged with CCR5-tropic HIV-1 showed profound CD4
+
T-cell loss. In contrast, mice transplanted with ZFN-modified HSPCs underwent rapid selection for
CCR5
−/−
cells, had significantly lower HIV-1 levels and preserved human cells throughout their tissues. The demonstration that a minority of
CCR5
−/−
HSPCs can populate an infected animal with HIV-1-resistant,
CCR5
−/−
progeny supports the use of ZFN-modified autologous hematopoietic stem cells as a clinical approach to treating HIV-1.</description><subject>631/532/1542</subject><subject>631/61/51/2315</subject><subject>692/699/249/1570/1901</subject><subject>Agriculture</subject><subject>AIDS treatment</subject><subject>Alleles</subject><subject>Animals</subject><subject>Autografts</subject><subject>B cells</subject><subject>Bioinformatics</subject><subject>Biological and medical sciences</subject><subject>Biomedical Engineering/Biotechnology</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Cells (Biology)</subject><subject>Cellular biology</subject><subject>Comparative analysis</subject><subject>Control</subject><subject>Development and progression</subject><subject>DNA binding proteins</subject><subject>Endonucleases - genetics</subject><subject>Endonucleases - metabolism</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Deletion</subject><subject>Gene expression</subject><subject>Gene therapy</subject><subject>Genetic aspects</subject><subject>Genetic Engineering - methods</subject><subject>Health aspects</subject><subject>Health. Pharmaceutical industry</subject><subject>Hematopoietic Stem Cell Transplantation - methods</subject><subject>Hematopoietic stem cells</subject><subject>Hematopoietic Stem Cells - metabolism</subject><subject>HIV</subject><subject>HIV infection</subject><subject>HIV Infections - immunology</subject><subject>HIV Infections - therapy</subject><subject>HIV Infections - virology</subject><subject>HIV-1 - immunology</subject><subject>HIV-1 - metabolism</subject><subject>Human immunodeficiency virus</subject><subject>Human immunodeficiency virus 1</subject><subject>Humans</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Infection</subject><subject>Life Sciences</subject><subject>Medical schools</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Miscellaneous</subject><subject>Nucleases</subject><subject>Physiological aspects</subject><subject>Properties</subject><subject>Receptors, CCR5 - genetics</subject><subject>Receptors, CCR5 - metabolism</subject><subject>Rodents</subject><subject>Stem cells</subject><subject>Stem Cells - metabolism</subject><subject>Surgery</subject><subject>T cells</subject><subject>T-Lymphocytes - immunology</subject><subject>T-Lymphocytes - metabolism</subject><subject>Zinc</subject><subject>Zinc finger proteins</subject><subject>Zinc Fingers - genetics</subject><subject>Zinc Fingers - physiology</subject><issn>1087-0156</issn><issn>1546-1696</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>N95</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqN02Fr1DAYB_AiiptT8BNIUEQFe0uaNE1fjkO9g8Fg6t6WNH3aZbTJLUmH89Obcqd3p6JHoQ3NL_8maZ4keU7wjGAqTk0dZoRz-iA5JjnjKeElfxjbWBQpJjk_Sp54f4Mx5ozzx8lRhjkmJS2PE7cYB2nQNQwy2JXVELRCPsBwunK2A6ODdUhB33s02Ea3GhpU36Pv2qi01aYDh8yoepAePArSdRCiCBbN55c5UtYEZ3u0WF6lBGmD7vSdfZo8amXv4dnmeZJ8_fjhy3yRnl98Ws7PzlMlCA4pE7ItWyJIIxsqFCEFqJZBwVResxxo7G9oW7MMCM5oQznFZaGgZg3FkCmgJ8mbdW5cye0IPlSD9tNSpAE7-koUjIiM8CzKl7_JGzs6EydXRcMoZoJG9GqNOtlDpU1rg5NqiqzOeEYELwqR_VNllJWUMcGimv1FxauBQcdNg1bH93sD3u0NmDYWvoVOjt5Xy8-X-1P4nz009-Lq8NzJ7ua-37H16LUBH29ed9fBr4fsRR_Ad9Pfrrly1nsHbbVyepDuviK4mgqiigVRTQUR6YvNrx3rAZpf8GcFRPB6A6RXsm-dNEr7raOEFZgV29X72DWd--0Z-eOjPwC7ahn_</recordid><startdate>20100801</startdate><enddate>20100801</enddate><creator>Holt, Nathalia</creator><creator>Wang, Jianbin</creator><creator>Kim, Kenneth</creator><creator>Friedman, Geoffrey</creator><creator>Wang, Xingchao</creator><creator>Taupin, Vanessa</creator><creator>Crooks, Gay M</creator><creator>Kohn, Donald B</creator><creator>Gregory, Philip D</creator><creator>Holmes, Michael C</creator><creator>Cannon, Paula M</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>IQODW</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>N95</scope><scope>XI7</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QO</scope><scope>7QP</scope><scope>7QR</scope><scope>7T7</scope><scope>7TK</scope><scope>7TM</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8AO</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>M2P</scope><scope>M7P</scope><scope>M7S</scope><scope>MBDVC</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>Q9U</scope><scope>RC3</scope></search><sort><creationdate>20100801</creationdate><title>Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo</title><author>Holt, Nathalia ; Wang, Jianbin ; Kim, Kenneth ; Friedman, Geoffrey ; Wang, Xingchao ; Taupin, Vanessa ; Crooks, Gay M ; Kohn, Donald B ; Gregory, Philip D ; Holmes, Michael C ; Cannon, Paula M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c810t-48af9f181dad38c117ecf4e74c5b45e348ad3fb42e1023d363097ceb4d30e2ce3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>631/532/1542</topic><topic>631/61/51/2315</topic><topic>692/699/249/1570/1901</topic><topic>Agriculture</topic><topic>AIDS treatment</topic><topic>Alleles</topic><topic>Animals</topic><topic>Autografts</topic><topic>B cells</topic><topic>Bioinformatics</topic><topic>Biological and medical sciences</topic><topic>Biomedical Engineering/Biotechnology</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Cells (Biology)</topic><topic>Cellular biology</topic><topic>Comparative analysis</topic><topic>Control</topic><topic>Development and progression</topic><topic>DNA binding proteins</topic><topic>Endonucleases - genetics</topic><topic>Endonucleases - metabolism</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Deletion</topic><topic>Gene expression</topic><topic>Gene therapy</topic><topic>Genetic aspects</topic><topic>Genetic Engineering - methods</topic><topic>Health aspects</topic><topic>Health. Pharmaceutical industry</topic><topic>Hematopoietic Stem Cell Transplantation - methods</topic><topic>Hematopoietic stem cells</topic><topic>Hematopoietic Stem Cells - metabolism</topic><topic>HIV</topic><topic>HIV infection</topic><topic>HIV Infections - immunology</topic><topic>HIV Infections - therapy</topic><topic>HIV Infections - virology</topic><topic>HIV-1 - immunology</topic><topic>HIV-1 - metabolism</topic><topic>Human immunodeficiency virus</topic><topic>Human immunodeficiency virus 1</topic><topic>Humans</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Infection</topic><topic>Life Sciences</topic><topic>Medical schools</topic><topic>Mice</topic><topic>Mice, Inbred NOD</topic><topic>Mice, SCID</topic><topic>Miscellaneous</topic><topic>Nucleases</topic><topic>Physiological aspects</topic><topic>Properties</topic><topic>Receptors, CCR5 - genetics</topic><topic>Receptors, CCR5 - metabolism</topic><topic>Rodents</topic><topic>Stem cells</topic><topic>Stem Cells - metabolism</topic><topic>Surgery</topic><topic>T cells</topic><topic>T-Lymphocytes - immunology</topic><topic>T-Lymphocytes - metabolism</topic><topic>Zinc</topic><topic>Zinc finger proteins</topic><topic>Zinc Fingers - genetics</topic><topic>Zinc Fingers - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Holt, Nathalia</creatorcontrib><creatorcontrib>Wang, Jianbin</creatorcontrib><creatorcontrib>Kim, Kenneth</creatorcontrib><creatorcontrib>Friedman, 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biotechnology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Holt, Nathalia</au><au>Wang, Jianbin</au><au>Kim, Kenneth</au><au>Friedman, Geoffrey</au><au>Wang, Xingchao</au><au>Taupin, Vanessa</au><au>Crooks, Gay M</au><au>Kohn, Donald B</au><au>Gregory, Philip D</au><au>Holmes, Michael C</au><au>Cannon, Paula M</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo</atitle><jtitle>Nature biotechnology</jtitle><stitle>Nat Biotechnol</stitle><addtitle>Nat Biotechnol</addtitle><date>2010-08-01</date><risdate>2010</risdate><volume>28</volume><issue>8</issue><spage>839</spage><epage>847</epage><pages>839-847</pages><issn>1087-0156</issn><eissn>1546-1696</eissn><coden>NABIF9</coden><abstract>Holt
et al
. describe an anti-HIV strategy in which human hematopoietic stem/progenitor cells are modified with zinc-finger nucleases to knock out the viral co-receptor CCR5. Transplantation of these cells into mice confers resistance to HIV, as shown by higher human T-cell counts and lower viral loads compared with animals that received unmodified cells.
CCR5 is the major HIV-1 co-receptor, and individuals homozygous for a 32-bp deletion in
CCR5
are resistant to infection by CCR5-tropic HIV-1. Using engineered zinc-finger nucleases (ZFNs), we disrupted
CCR5
in human CD34
+
hematopoietic stem/progenitor cells (HSPCs) at a mean frequency of 17% of the total alleles in a population. This procedure produces both mono- and bi-allelically disrupted cells. ZFN-treated HSPCs retained the ability to engraft NOD/SCID/IL2rγ
null
mice and gave rise to polyclonal multi-lineage progeny in which
CCR5
was permanently disrupted. Control mice receiving untreated HSPCs and challenged with CCR5-tropic HIV-1 showed profound CD4
+
T-cell loss. In contrast, mice transplanted with ZFN-modified HSPCs underwent rapid selection for
CCR5
−/−
cells, had significantly lower HIV-1 levels and preserved human cells throughout their tissues. The demonstration that a minority of
CCR5
−/−
HSPCs can populate an infected animal with HIV-1-resistant,
CCR5
−/−
progeny supports the use of ZFN-modified autologous hematopoietic stem cells as a clinical approach to treating HIV-1.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>20601939</pmid><doi>10.1038/nbt.1663</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1087-0156 |
| ispartof | Nature biotechnology, 2010-08, Vol.28 (8), p.839-847 |
| issn | 1087-0156 1546-1696 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_874182162 |
| source | MEDLINE; SpringerLink Journals; Nature Journals Online |
| subjects | 631/532/1542 631/61/51/2315 692/699/249/1570/1901 Agriculture AIDS treatment Alleles Animals Autografts B cells Bioinformatics Biological and medical sciences Biomedical Engineering/Biotechnology Biomedicine Biotechnology Cells (Biology) Cellular biology Comparative analysis Control Development and progression DNA binding proteins Endonucleases - genetics Endonucleases - metabolism Fundamental and applied biological sciences. Psychology Gene Deletion Gene expression Gene therapy Genetic aspects Genetic Engineering - methods Health aspects Health. Pharmaceutical industry Hematopoietic Stem Cell Transplantation - methods Hematopoietic stem cells Hematopoietic Stem Cells - metabolism HIV HIV infection HIV Infections - immunology HIV Infections - therapy HIV Infections - virology HIV-1 - immunology HIV-1 - metabolism Human immunodeficiency virus Human immunodeficiency virus 1 Humans Industrial applications and implications. Economical aspects Infection Life Sciences Medical schools Mice Mice, Inbred NOD Mice, SCID Miscellaneous Nucleases Physiological aspects Properties Receptors, CCR5 - genetics Receptors, CCR5 - metabolism Rodents Stem cells Stem Cells - metabolism Surgery T cells T-Lymphocytes - immunology T-Lymphocytes - metabolism Zinc Zinc finger proteins Zinc Fingers - genetics Zinc Fingers - physiology |
| title | Human hematopoietic stem/progenitor cells modified by zinc-finger nucleases targeted to CCR5 control HIV-1 in vivo |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-19T10%3A19%3A03IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Human%20hematopoietic%20stem/progenitor%20cells%20modified%20by%20zinc-finger%20nucleases%20targeted%20to%20CCR5%20control%20HIV-1%20in%20vivo&rft.jtitle=Nature%20biotechnology&rft.au=Holt,%20Nathalia&rft.date=2010-08-01&rft.volume=28&rft.issue=8&rft.spage=839&rft.epage=847&rft.pages=839-847&rft.issn=1087-0156&rft.eissn=1546-1696&rft.coden=NABIF9&rft_id=info:doi/10.1038/nbt.1663&rft_dat=%3Cgale_proqu%3EA234934484%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=741430483&rft_id=info:pmid/20601939&rft_galeid=A234934484&rfr_iscdi=true |