Efficient and stable transduction of dopaminergic neurons in rat substantia nigra by rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9
Dysfunction of the nigrostriatal system is the major cause of Parkinson's disease (PD). This brain region is therefore an important target for gene delivery aiming at disease modeling and gene therapy. Recombinant adeno-associated viral (rAAV) vectors have been developed as efficient vehicles f...
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| description | Dysfunction of the nigrostriatal system is the major cause of Parkinson's disease (PD). This brain region is therefore an important target for gene delivery aiming at disease modeling and gene therapy. Recombinant adeno-associated viral (rAAV) vectors have been developed as efficient vehicles for gene transfer into the central nervous system. Recently, several serotypes have been described, with varying tropism for brain transduction. In light of the further development of a viral vector-mediated rat model for PD, we performed a comprehensive comparison of the transduction and tropism for dopaminergic neurons (DNs) in the adult Wistar rat substantia nigra (SN) of seven rAAV vector serotypes (rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9). All vectors were normalized by titer and volume, and stereotactically injected into the SN. Gene expression was assessed non-invasively and quantitatively
in vivo
by bioluminescence imaging at 2 and 5 weeks after injection, and was found to be stable over time. Immunohistochemistry at 6 weeks following injection revealed the most widespread enhanced green fluorescence protein expression and the highest number of positive nigral cells using rAAV 2/7, 2/9 and 2/1. The area transduced by rAAV 2/8 was smaller, but nevertheless almost equal numbers of nigral cells were targeted. Detailed confocal analysis revealed that serotype 2/7, 2/9, 2/1 and 2/8 transduced at least 70% of the DNs. In conclusion, these results show that various rAAV serotypes efficiently transduce nigral DNs, but significant differences in transgene expression pattern and level were observed. |
| doi_str_mv | 10.1038/gt.2010.179 |
| format | Article |
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in vivo
by bioluminescence imaging at 2 and 5 weeks after injection, and was found to be stable over time. Immunohistochemistry at 6 weeks following injection revealed the most widespread enhanced green fluorescence protein expression and the highest number of positive nigral cells using rAAV 2/7, 2/9 and 2/1. The area transduced by rAAV 2/8 was smaller, but nevertheless almost equal numbers of nigral cells were targeted. Detailed confocal analysis revealed that serotype 2/7, 2/9, 2/1 and 2/8 transduced at least 70% of the DNs. In conclusion, these results show that various rAAV serotypes efficiently transduce nigral DNs, but significant differences in transgene expression pattern and level were observed.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/gt.2010.179</identifier><identifier>PMID: 21326331</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/1647/2300/1850 ; 631/326/596/2561 ; 692/698/1688/64 ; 692/699/375/346/1718 ; Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy ; Animal models ; Animals ; Applied cell therapy and gene therapy ; Biological and medical sciences ; Bioluminescence ; Biomedical and Life Sciences ; Biomedicine ; Biotechnology ; Care and treatment ; Cell Biology ; Central nervous system ; Dependovirus - genetics ; Dopamine ; Dopamine - metabolism ; Dopamine receptors ; Expression vectors ; Fundamental and applied biological sciences. Psychology ; Gene Expression ; Gene Therapy ; Gene transfer ; Genetic aspects ; Genetic Vectors ; Green Fluorescent Proteins - genetics ; Green Fluorescent Proteins - metabolism ; Health aspects ; Health. Pharmaceutical industry ; Human Genetics ; Immunohistochemistry ; Industrial applications and implications. Economical aspects ; Injection ; Medical sciences ; Movement disorders ; Nanotechnology ; Neurodegenerative diseases ; Neuroimaging ; Neurons ; original-article ; Parkinson's disease ; Physiological aspects ; Rats ; Rats, Wistar ; Serotypes ; Serotyping ; Substantia nigra ; Substantia Nigra - cytology ; Substantia Nigra - metabolism ; Transduction ; Transduction, Genetic ; Transfusions. Complications. Transfusion reactions. Cell and gene therapy ; Tropism</subject><ispartof>Gene therapy, 2011-05, Vol.18 (5), p.517-527</ispartof><rights>Macmillan Publishers Limited 2011</rights><rights>2015 INIST-CNRS</rights><rights>COPYRIGHT 2011 Nature Publishing Group</rights><rights>Macmillan Publishers Limited 2011.</rights><rights>Copyright Nature Publishing Group May 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c611t-eeba2a5ae0cef118e9f600d8481e4e6a14076d4d12aa6691554b5226d20b75a73</citedby><cites>FETCH-LOGICAL-c611t-eeba2a5ae0cef118e9f600d8481e4e6a14076d4d12aa6691554b5226d20b75a73</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/gt.2010.179$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/gt.2010.179$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=24138335$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/21326331$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Van der Perren, A</creatorcontrib><creatorcontrib>Toelen, J</creatorcontrib><creatorcontrib>Carlon, M</creatorcontrib><creatorcontrib>Van den Haute, C</creatorcontrib><creatorcontrib>Coun, F</creatorcontrib><creatorcontrib>Heeman, B</creatorcontrib><creatorcontrib>Reumers, V</creatorcontrib><creatorcontrib>Vandenberghe, L H</creatorcontrib><creatorcontrib>Wilson, J M</creatorcontrib><creatorcontrib>Debyser, Z</creatorcontrib><creatorcontrib>Baekelandt, V</creatorcontrib><title>Efficient and stable transduction of dopaminergic neurons in rat substantia nigra by rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>Dysfunction of the nigrostriatal system is the major cause of Parkinson's disease (PD). This brain region is therefore an important target for gene delivery aiming at disease modeling and gene therapy. Recombinant adeno-associated viral (rAAV) vectors have been developed as efficient vehicles for gene transfer into the central nervous system. Recently, several serotypes have been described, with varying tropism for brain transduction. In light of the further development of a viral vector-mediated rat model for PD, we performed a comprehensive comparison of the transduction and tropism for dopaminergic neurons (DNs) in the adult Wistar rat substantia nigra (SN) of seven rAAV vector serotypes (rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9). All vectors were normalized by titer and volume, and stereotactically injected into the SN. Gene expression was assessed non-invasively and quantitatively
in vivo
by bioluminescence imaging at 2 and 5 weeks after injection, and was found to be stable over time. Immunohistochemistry at 6 weeks following injection revealed the most widespread enhanced green fluorescence protein expression and the highest number of positive nigral cells using rAAV 2/7, 2/9 and 2/1. The area transduced by rAAV 2/8 was smaller, but nevertheless almost equal numbers of nigral cells were targeted. Detailed confocal analysis revealed that serotype 2/7, 2/9, 2/1 and 2/8 transduced at least 70% of the DNs. In conclusion, these results show that various rAAV serotypes efficiently transduce nigral DNs, but significant differences in transgene expression pattern and level were observed.</description><subject>631/1647/2300/1850</subject><subject>631/326/596/2561</subject><subject>692/698/1688/64</subject><subject>692/699/375/346/1718</subject><subject>Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy</subject><subject>Animal models</subject><subject>Animals</subject><subject>Applied cell therapy and gene therapy</subject><subject>Biological and medical sciences</subject><subject>Bioluminescence</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Biotechnology</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Central nervous system</subject><subject>Dependovirus - genetics</subject><subject>Dopamine</subject><subject>Dopamine - metabolism</subject><subject>Dopamine receptors</subject><subject>Expression vectors</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>Gene Expression</subject><subject>Gene Therapy</subject><subject>Gene transfer</subject><subject>Genetic aspects</subject><subject>Genetic Vectors</subject><subject>Green Fluorescent Proteins - genetics</subject><subject>Green Fluorescent Proteins - metabolism</subject><subject>Health aspects</subject><subject>Health. Pharmaceutical industry</subject><subject>Human Genetics</subject><subject>Immunohistochemistry</subject><subject>Industrial applications and implications. Economical aspects</subject><subject>Injection</subject><subject>Medical sciences</subject><subject>Movement disorders</subject><subject>Nanotechnology</subject><subject>Neurodegenerative diseases</subject><subject>Neuroimaging</subject><subject>Neurons</subject><subject>original-article</subject><subject>Parkinson's disease</subject><subject>Physiological aspects</subject><subject>Rats</subject><subject>Rats, Wistar</subject><subject>Serotypes</subject><subject>Serotyping</subject><subject>Substantia nigra</subject><subject>Substantia Nigra - cytology</subject><subject>Substantia Nigra - metabolism</subject><subject>Transduction</subject><subject>Transduction, Genetic</subject><subject>Transfusions. Complications. Transfusion reactions. 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Intensive care medicine. Transfusions. Cell therapy and gene therapy</topic><topic>Animal models</topic><topic>Animals</topic><topic>Applied cell therapy and gene therapy</topic><topic>Biological and medical sciences</topic><topic>Bioluminescence</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Biotechnology</topic><topic>Care and treatment</topic><topic>Cell Biology</topic><topic>Central nervous system</topic><topic>Dependovirus - genetics</topic><topic>Dopamine</topic><topic>Dopamine - metabolism</topic><topic>Dopamine receptors</topic><topic>Expression vectors</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>Gene Expression</topic><topic>Gene Therapy</topic><topic>Gene transfer</topic><topic>Genetic aspects</topic><topic>Genetic Vectors</topic><topic>Green Fluorescent Proteins - genetics</topic><topic>Green Fluorescent Proteins - metabolism</topic><topic>Health aspects</topic><topic>Health. Pharmaceutical industry</topic><topic>Human Genetics</topic><topic>Immunohistochemistry</topic><topic>Industrial applications and implications. Economical aspects</topic><topic>Injection</topic><topic>Medical sciences</topic><topic>Movement disorders</topic><topic>Nanotechnology</topic><topic>Neurodegenerative diseases</topic><topic>Neuroimaging</topic><topic>Neurons</topic><topic>original-article</topic><topic>Parkinson's disease</topic><topic>Physiological aspects</topic><topic>Rats</topic><topic>Rats, Wistar</topic><topic>Serotypes</topic><topic>Serotyping</topic><topic>Substantia nigra</topic><topic>Substantia Nigra - cytology</topic><topic>Substantia Nigra - metabolism</topic><topic>Transduction</topic><topic>Transduction, Genetic</topic><topic>Transfusions. Complications. Transfusion reactions. 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This brain region is therefore an important target for gene delivery aiming at disease modeling and gene therapy. Recombinant adeno-associated viral (rAAV) vectors have been developed as efficient vehicles for gene transfer into the central nervous system. Recently, several serotypes have been described, with varying tropism for brain transduction. In light of the further development of a viral vector-mediated rat model for PD, we performed a comprehensive comparison of the transduction and tropism for dopaminergic neurons (DNs) in the adult Wistar rat substantia nigra (SN) of seven rAAV vector serotypes (rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9). All vectors were normalized by titer and volume, and stereotactically injected into the SN. Gene expression was assessed non-invasively and quantitatively
in vivo
by bioluminescence imaging at 2 and 5 weeks after injection, and was found to be stable over time. Immunohistochemistry at 6 weeks following injection revealed the most widespread enhanced green fluorescence protein expression and the highest number of positive nigral cells using rAAV 2/7, 2/9 and 2/1. The area transduced by rAAV 2/8 was smaller, but nevertheless almost equal numbers of nigral cells were targeted. Detailed confocal analysis revealed that serotype 2/7, 2/9, 2/1 and 2/8 transduced at least 70% of the DNs. In conclusion, these results show that various rAAV serotypes efficiently transduce nigral DNs, but significant differences in transgene expression pattern and level were observed.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>21326331</pmid><doi>10.1038/gt.2010.179</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0969-7128 |
| ispartof | Gene therapy, 2011-05, Vol.18 (5), p.517-527 |
| issn | 0969-7128 1476-5462 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_874197171 |
| source | MEDLINE; Springer Nature - Complete Springer Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | 631/1647/2300/1850 631/326/596/2561 692/698/1688/64 692/699/375/346/1718 Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy Animal models Animals Applied cell therapy and gene therapy Biological and medical sciences Bioluminescence Biomedical and Life Sciences Biomedicine Biotechnology Care and treatment Cell Biology Central nervous system Dependovirus - genetics Dopamine Dopamine - metabolism Dopamine receptors Expression vectors Fundamental and applied biological sciences. Psychology Gene Expression Gene Therapy Gene transfer Genetic aspects Genetic Vectors Green Fluorescent Proteins - genetics Green Fluorescent Proteins - metabolism Health aspects Health. Pharmaceutical industry Human Genetics Immunohistochemistry Industrial applications and implications. Economical aspects Injection Medical sciences Movement disorders Nanotechnology Neurodegenerative diseases Neuroimaging Neurons original-article Parkinson's disease Physiological aspects Rats Rats, Wistar Serotypes Serotyping Substantia nigra Substantia Nigra - cytology Substantia Nigra - metabolism Transduction Transduction, Genetic Transfusions. Complications. Transfusion reactions. Cell and gene therapy Tropism |
| title | Efficient and stable transduction of dopaminergic neurons in rat substantia nigra by rAAV 2/1, 2/2, 2/5, 2/6.2, 2/7, 2/8 and 2/9 |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T23%3A05%3A49IST&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=Efficient%20and%20stable%20transduction%20of%20dopaminergic%20neurons%20in%20rat%20substantia%20nigra%20by%20rAAV%202/1,%202/2,%202/5,%202/6.2,%202/7,%202/8%20and%202/9&rft.jtitle=Gene%20therapy&rft.au=Van%20der%20Perren,%20A&rft.date=2011-05-01&rft.volume=18&rft.issue=5&rft.spage=517&rft.epage=527&rft.pages=517-527&rft.issn=0969-7128&rft.eissn=1476-5462&rft_id=info:doi/10.1038/gt.2010.179&rft_dat=%3Cgale_proqu%3EA257127752%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=2644671951&rft_id=info:pmid/21326331&rft_galeid=A257127752&rfr_iscdi=true |