Noninvasive tracking of gene transcript and neuroprotection after gene therapy
Gene therapy holds exceptional potential for translational medicine by improving the products of defective genes in diseases and/or providing necessary biologics from endogenous sources during recovery processes. However, validating methods for the delivery, distribution and expression of the exogen...
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| Veröffentlicht in: | Gene therapy 2016-01, Vol.23 (1), p.1-9 |
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| creator | Ren, J Chen, Y I Liu, C H Chen, P-C Prentice, H Wu, J-Y Liu, P K |
| description | Gene therapy holds exceptional potential for translational medicine by improving the products of defective genes in diseases and/or providing necessary biologics from endogenous sources during recovery processes. However, validating methods for the delivery, distribution and expression of the exogenous genes from such therapy can generally not be applicable to monitor effects over the long term because they are invasive. We report here that human granulocyte colony-stimulating factor (hG-CSF) complimentary DNA (cDNA) encoded in self-complementary adeno-associated virus-type 2 adeno-associated virus, as delivered through eye drops at multiple time points after cerebral ischemia using bilateral carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality rates, cerebral atrophy and neurological deficits in C57black6 mice. Most importantly, we validated hG-CSF cDNA expression using translatable magnetic resonance imaging (MRI) in living brains. This noninvasive approach for monitoring exogenous gene expression in the brains has potential for great impact in the area of experimental gene therapy in animal models of heart attack, stroke, Alzheimer’s dementia, Parkinson’s disorder and amyotrophic lateral sclerosis, and the translation of such techniques to emergency medicine. |
| doi_str_mv | 10.1038/gt.2015.81 |
| format | Article |
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However, validating methods for the delivery, distribution and expression of the exogenous genes from such therapy can generally not be applicable to monitor effects over the long term because they are invasive. We report here that human granulocyte colony-stimulating factor (hG-CSF) complimentary DNA (cDNA) encoded in self-complementary adeno-associated virus-type 2 adeno-associated virus, as delivered through eye drops at multiple time points after cerebral ischemia using bilateral carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality rates, cerebral atrophy and neurological deficits in C57black6 mice. Most importantly, we validated hG-CSF cDNA expression using translatable magnetic resonance imaging (MRI) in living brains. This noninvasive approach for monitoring exogenous gene expression in the brains has potential for great impact in the area of experimental gene therapy in animal models of heart attack, stroke, Alzheimer’s dementia, Parkinson’s disorder and amyotrophic lateral sclerosis, and the translation of such techniques to emergency medicine.</description><identifier>ISSN: 0969-7128</identifier><identifier>EISSN: 1476-5462</identifier><identifier>DOI: 10.1038/gt.2015.81</identifier><identifier>PMID: 26207935</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>38/39 ; 42/41 ; 45/71 ; 59/57 ; 631/1647/2300 ; 631/61/51/201 ; 64/60 ; 692/308/575 ; 692/699/375 ; 82/51 ; 96/44 ; Adeno-associated virus ; Alzheimer's disease ; Animals ; Biological products ; Biomedical and Life Sciences ; Biomedicine ; Brain - metabolism ; Brain Ischemia - pathology ; Brain Ischemia - therapy ; Care and treatment ; Cell Biology ; Cerebrum - pathology ; Dependovirus - genetics ; Dependoviruses ; Disease Models, Animal ; DNA, Complementary - genetics ; DNA, Complementary - metabolism ; Gene Expression ; Gene Expression Regulation ; Gene Therapy ; Genetic aspects ; Genetic research ; Genetic Therapy - methods ; Genetic Vectors ; Granulocyte colony-stimulating factor ; Granulocyte Colony-Stimulating Factor - genetics ; Granulocyte Colony-Stimulating Factor - metabolism ; Health aspects ; Human Genetics ; Humans ; Immunohistochemistry ; Ischemia ; Magnetic Resonance Imaging ; Male ; Methods ; Mice ; Mice, Inbred C57BL ; Nanotechnology ; Neuroprotection ; Ophthalmic Solutions ; original-article-enabling-technologies ; Patient outcomes ; PC12 Cells ; Phosphorothioate Oligonucleotides - genetics ; Rats ; Transcription factors</subject><ispartof>Gene therapy, 2016-01, Vol.23 (1), p.1-9</ispartof><rights>Macmillan Publishers Limited 2016</rights><rights>COPYRIGHT 2016 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Jan 2016</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c770t-68867006080a08335a97d46b7802a55d5a92e8f5bd13b19c08131ec071da1bb63</citedby><cites>FETCH-LOGICAL-c770t-68867006080a08335a97d46b7802a55d5a92e8f5bd13b19c08131ec071da1bb63</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.2015.81$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1038/gt.2015.81$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>230,314,776,780,881,27903,27904,41467,42536,51297</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26207935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ren, J</creatorcontrib><creatorcontrib>Chen, Y I</creatorcontrib><creatorcontrib>Liu, C H</creatorcontrib><creatorcontrib>Chen, P-C</creatorcontrib><creatorcontrib>Prentice, H</creatorcontrib><creatorcontrib>Wu, J-Y</creatorcontrib><creatorcontrib>Liu, P K</creatorcontrib><title>Noninvasive tracking of gene transcript and neuroprotection after gene therapy</title><title>Gene therapy</title><addtitle>Gene Ther</addtitle><addtitle>Gene Ther</addtitle><description>Gene therapy holds exceptional potential for translational medicine by improving the products of defective genes in diseases and/or providing necessary biologics from endogenous sources during recovery processes. However, validating methods for the delivery, distribution and expression of the exogenous genes from such therapy can generally not be applicable to monitor effects over the long term because they are invasive. We report here that human granulocyte colony-stimulating factor (hG-CSF) complimentary DNA (cDNA) encoded in self-complementary adeno-associated virus-type 2 adeno-associated virus, as delivered through eye drops at multiple time points after cerebral ischemia using bilateral carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality rates, cerebral atrophy and neurological deficits in C57black6 mice. Most importantly, we validated hG-CSF cDNA expression using translatable magnetic resonance imaging (MRI) in living brains. This noninvasive approach for monitoring exogenous gene expression in the brains has potential for great impact in the area of experimental gene therapy in animal models of heart attack, stroke, Alzheimer’s dementia, Parkinson’s disorder and amyotrophic lateral sclerosis, and the translation of such techniques to emergency medicine.</description><subject>38/39</subject><subject>42/41</subject><subject>45/71</subject><subject>59/57</subject><subject>631/1647/2300</subject><subject>631/61/51/201</subject><subject>64/60</subject><subject>692/308/575</subject><subject>692/699/375</subject><subject>82/51</subject><subject>96/44</subject><subject>Adeno-associated virus</subject><subject>Alzheimer's disease</subject><subject>Animals</subject><subject>Biological products</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Brain - metabolism</subject><subject>Brain Ischemia - pathology</subject><subject>Brain Ischemia - therapy</subject><subject>Care and treatment</subject><subject>Cell Biology</subject><subject>Cerebrum - 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genetics</topic><topic>Rats</topic><topic>Transcription factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ren, J</creatorcontrib><creatorcontrib>Chen, Y I</creatorcontrib><creatorcontrib>Liu, C H</creatorcontrib><creatorcontrib>Chen, P-C</creatorcontrib><creatorcontrib>Prentice, H</creatorcontrib><creatorcontrib>Wu, J-Y</creatorcontrib><creatorcontrib>Liu, P K</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Gale In Context: Science</collection><collection>ProQuest Central (Corporate)</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>Nucleic Acids Abstracts</collection><collection>Virology and AIDS Abstracts</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Public Health Database</collection><collection>Technology Research Database</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>Research Library (Alumni Edition)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Engineering Research Database</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>Research Library Prep</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Research Library</collection><collection>Biological Science Database</collection><collection>Research Library (Corporate)</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>ProQuest Central Basic</collection><collection>Genetics Abstracts</collection><collection>MEDLINE - Academic</collection><collection>Biotechnology Research Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Gene therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ren, J</au><au>Chen, Y I</au><au>Liu, C H</au><au>Chen, P-C</au><au>Prentice, H</au><au>Wu, J-Y</au><au>Liu, P K</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Noninvasive tracking of gene transcript and neuroprotection after gene therapy</atitle><jtitle>Gene therapy</jtitle><stitle>Gene Ther</stitle><addtitle>Gene Ther</addtitle><date>2016-01-01</date><risdate>2016</risdate><volume>23</volume><issue>1</issue><spage>1</spage><epage>9</epage><pages>1-9</pages><issn>0969-7128</issn><eissn>1476-5462</eissn><abstract>Gene therapy holds exceptional potential for translational medicine by improving the products of defective genes in diseases and/or providing necessary biologics from endogenous sources during recovery processes. However, validating methods for the delivery, distribution and expression of the exogenous genes from such therapy can generally not be applicable to monitor effects over the long term because they are invasive. We report here that human granulocyte colony-stimulating factor (hG-CSF) complimentary DNA (cDNA) encoded in self-complementary adeno-associated virus-type 2 adeno-associated virus, as delivered through eye drops at multiple time points after cerebral ischemia using bilateral carotid occlusion for 60 min (BCAO-60) led to significant reduction in mortality rates, cerebral atrophy and neurological deficits in C57black6 mice. Most importantly, we validated hG-CSF cDNA expression using translatable magnetic resonance imaging (MRI) in living brains. This noninvasive approach for monitoring exogenous gene expression in the brains has potential for great impact in the area of experimental gene therapy in animal models of heart attack, stroke, Alzheimer’s dementia, Parkinson’s disorder and amyotrophic lateral sclerosis, and the translation of such techniques to emergency medicine.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26207935</pmid><doi>10.1038/gt.2015.81</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Gene therapy, 2016-01, Vol.23 (1), p.1-9 |
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| subjects | 38/39 42/41 45/71 59/57 631/1647/2300 631/61/51/201 64/60 692/308/575 692/699/375 82/51 96/44 Adeno-associated virus Alzheimer's disease Animals Biological products Biomedical and Life Sciences Biomedicine Brain - metabolism Brain Ischemia - pathology Brain Ischemia - therapy Care and treatment Cell Biology Cerebrum - pathology Dependovirus - genetics Dependoviruses Disease Models, Animal DNA, Complementary - genetics DNA, Complementary - metabolism Gene Expression Gene Expression Regulation Gene Therapy Genetic aspects Genetic research Genetic Therapy - methods Genetic Vectors Granulocyte colony-stimulating factor Granulocyte Colony-Stimulating Factor - genetics Granulocyte Colony-Stimulating Factor - metabolism Health aspects Human Genetics Humans Immunohistochemistry Ischemia Magnetic Resonance Imaging Male Methods Mice Mice, Inbred C57BL Nanotechnology Neuroprotection Ophthalmic Solutions original-article-enabling-technologies Patient outcomes PC12 Cells Phosphorothioate Oligonucleotides - genetics Rats Transcription factors |
| title | Noninvasive tracking of gene transcript and neuroprotection after gene therapy |
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