Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing
Conventional gene therapy of hemophilia A relies on the transfer of factor VIII (FVIII; encoded by the F8 gene) cDNA. We carried out spliceosome-mediated RNA trans -splicing (SMaRT) to repair mutant FVIII mRNA. A pre- trans -splicing molecule (PTM) corrected endogenous FVIII mRNA in F8 knockout mice...
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| Veröffentlicht in: | Nature medicine 2003-08, Vol.9 (8), p.1015-1019 |
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| creator | Chao, Hengjun Mansfield, S Gary Bartel, Robert C Hiriyanna, Suja Mitchell, Lloyd G Garcia-Blanco, Mariano A Walsh, Christopher E |
| description | Conventional gene therapy of hemophilia A relies on the transfer of factor VIII (FVIII; encoded by the
F8
gene) cDNA. We carried out spliceosome-mediated RNA
trans
-splicing (SMaRT) to repair mutant FVIII mRNA. A pre-
trans
-splicing molecule (PTM) corrected endogenous FVIII mRNA in
F8
knockout mice with the hemophilia A phenotype, producing sufficient functional FVIII to correct the hemophilia A phenotype. This is the first description of phenotypic correction of a genetic defect by RNA repair in a knockout animal model. Our results indicate the feasibility of using SMaRT to repair RNA for the treatment of genetic diseases. |
| doi_str_mv | 10.1038/nm900 |
| format | Article |
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F8
gene) cDNA. We carried out spliceosome-mediated RNA
trans
-splicing (SMaRT) to repair mutant FVIII mRNA. A pre-
trans
-splicing molecule (PTM) corrected endogenous FVIII mRNA in
F8
knockout mice with the hemophilia A phenotype, producing sufficient functional FVIII to correct the hemophilia A phenotype. This is the first description of phenotypic correction of a genetic defect by RNA repair in a knockout animal model. Our results indicate the feasibility of using SMaRT to repair RNA for the treatment of genetic diseases.</description><identifier>ISSN: 1078-8956</identifier><identifier>EISSN: 1546-170X</identifier><identifier>DOI: 10.1038/nm900</identifier><identifier>PMID: 12847523</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>Animal models ; Animals ; Biomedical and Life Sciences ; Biomedicine ; Blood Coagulation - physiology ; Cancer Research ; Cell Line ; Disease Models, Animal ; Factor VIII - genetics ; Factor VIII - metabolism ; Genetic Therapy - methods ; Hemophilia ; Hemophilia A - genetics ; Hemophilia A - therapy ; Humans ; Infectious Diseases ; Metabolic Diseases ; Mice ; Mice, Knockout ; Molecular Medicine ; Neurosciences ; Phenotype ; RNA - genetics ; RNA - metabolism ; RNA Splicing ; Spliceosomes - metabolism</subject><ispartof>Nature medicine, 2003-08, Vol.9 (8), p.1015-1019</ispartof><rights>Springer Nature America, Inc. 2003</rights><rights>COPYRIGHT 2003 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2003</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c604t-5cf7d75a58aaa8e3c4ae0495497641f7fc45bd8b3857d0036d8208fc8c61dec03</citedby><cites>FETCH-LOGICAL-c604t-5cf7d75a58aaa8e3c4ae0495497641f7fc45bd8b3857d0036d8208fc8c61dec03</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/nm900$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/nm900$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/12847523$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Chao, Hengjun</creatorcontrib><creatorcontrib>Mansfield, S Gary</creatorcontrib><creatorcontrib>Bartel, Robert C</creatorcontrib><creatorcontrib>Hiriyanna, Suja</creatorcontrib><creatorcontrib>Mitchell, Lloyd G</creatorcontrib><creatorcontrib>Garcia-Blanco, Mariano A</creatorcontrib><creatorcontrib>Walsh, Christopher E</creatorcontrib><title>Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing</title><title>Nature medicine</title><addtitle>Nat Med</addtitle><addtitle>Nat Med</addtitle><description>Conventional gene therapy of hemophilia A relies on the transfer of factor VIII (FVIII; encoded by the
F8
gene) cDNA. We carried out spliceosome-mediated RNA
trans
-splicing (SMaRT) to repair mutant FVIII mRNA. A pre-
trans
-splicing molecule (PTM) corrected endogenous FVIII mRNA in
F8
knockout mice with the hemophilia A phenotype, producing sufficient functional FVIII to correct the hemophilia A phenotype. This is the first description of phenotypic correction of a genetic defect by RNA repair in a knockout animal model. Our results indicate the feasibility of using SMaRT to repair RNA for the treatment of genetic diseases.</description><subject>Animal models</subject><subject>Animals</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Blood Coagulation - physiology</subject><subject>Cancer Research</subject><subject>Cell Line</subject><subject>Disease Models, Animal</subject><subject>Factor VIII - genetics</subject><subject>Factor VIII - metabolism</subject><subject>Genetic Therapy - methods</subject><subject>Hemophilia</subject><subject>Hemophilia A - genetics</subject><subject>Hemophilia A - therapy</subject><subject>Humans</subject><subject>Infectious Diseases</subject><subject>Metabolic Diseases</subject><subject>Mice</subject><subject>Mice, Knockout</subject><subject>Molecular Medicine</subject><subject>Neurosciences</subject><subject>Phenotype</subject><subject>RNA - genetics</subject><subject>RNA - metabolism</subject><subject>RNA Splicing</subject><subject>Spliceosomes - 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Academic</collection><jtitle>Nature medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Chao, Hengjun</au><au>Mansfield, S Gary</au><au>Bartel, Robert C</au><au>Hiriyanna, Suja</au><au>Mitchell, Lloyd G</au><au>Garcia-Blanco, Mariano A</au><au>Walsh, Christopher E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing</atitle><jtitle>Nature medicine</jtitle><stitle>Nat Med</stitle><addtitle>Nat Med</addtitle><date>2003-08-01</date><risdate>2003</risdate><volume>9</volume><issue>8</issue><spage>1015</spage><epage>1019</epage><pages>1015-1019</pages><issn>1078-8956</issn><eissn>1546-170X</eissn><abstract>Conventional gene therapy of hemophilia A relies on the transfer of factor VIII (FVIII; encoded by the
F8
gene) cDNA. We carried out spliceosome-mediated RNA
trans
-splicing (SMaRT) to repair mutant FVIII mRNA. A pre-
trans
-splicing molecule (PTM) corrected endogenous FVIII mRNA in
F8
knockout mice with the hemophilia A phenotype, producing sufficient functional FVIII to correct the hemophilia A phenotype. This is the first description of phenotypic correction of a genetic defect by RNA repair in a knockout animal model. Our results indicate the feasibility of using SMaRT to repair RNA for the treatment of genetic diseases.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>12847523</pmid><doi>10.1038/nm900</doi><tpages>5</tpages></addata></record> |
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| issn | 1078-8956 1546-170X |
| language | eng |
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| source | MEDLINE; Springer Nature - Complete Springer Journals; Nature Journals Online |
| subjects | Animal models Animals Biomedical and Life Sciences Biomedicine Blood Coagulation - physiology Cancer Research Cell Line Disease Models, Animal Factor VIII - genetics Factor VIII - metabolism Genetic Therapy - methods Hemophilia Hemophilia A - genetics Hemophilia A - therapy Humans Infectious Diseases Metabolic Diseases Mice Mice, Knockout Molecular Medicine Neurosciences Phenotype RNA - genetics RNA - metabolism RNA Splicing Spliceosomes - metabolism |
| title | Phenotype correction of hemophilia A mice by spliceosome-mediated RNA trans-splicing |
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