Analysis of AAV Serotypes 1–9 Mediated Gene Expression and Tropism in Mice After Systemic Injection
This study examines transgene expression and biodistribution of adeno-associated virus (AAV) pseudotyped 1–9 after tail vein (TV) injection in male mice. Using a cytomegalovirus (CMV)-luciferase transgene, the time-course of expression in each animal was tracked throughout the experiment. The animal...
Gespeichert in:
| Veröffentlicht in: | Molecular therapy 2008-06, Vol.16 (6), p.1073-1080 |
|---|---|
| Hauptverfasser: | , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 1080 |
|---|---|
| container_issue | 6 |
| container_start_page | 1073 |
| container_title | Molecular therapy |
| container_volume | 16 |
| creator | Zincarelli, Carmela Soltys, Stephen Rengo, Giuseppe Rabinowitz, Joseph E |
| description | This study examines transgene expression and biodistribution of adeno-associated virus (AAV) pseudotyped 1–9 after tail vein (TV) injection in male mice. Using a cytomegalovirus (CMV)-luciferase transgene, the time-course of expression in each animal was tracked throughout the experiment. The animals were imaged at 7, 14, 29, 56, and 100 days after the TV injection. The total number of photons emitted from each animal was recorded, allowing examination of expression level and kinetics for each pseudotyped virus. The bioluminescence imaging revealed three expression levels (i) low-expression group, AAV2, 3, 4, and 5; (ii) moderate-expression group, AAV1, 6, and 8; and (iii) high-expression group, AAV7 and 9. In addition, imaging revealed two classes of kinetics (i) rapid-onset, for AAV1, 6, 7, 8, and 9; and (ii) slow-onset, for AAV2, 3, 4, and 5. We next evaluated protein expression and viral genome copy numbers in dissected tissues. AAV9 had the best viral genome distribution and highest protein levels. The AAV7 protein and genome copy numbers were comparable to those of AAV9 in the liver. Most surprisingly, AAV4 showed the greatest number of genome copies in lung and kidney, and a high copy number in the heart. AAV6 expression was observed in the heart, liver, and skeletal muscle, and the genome distribution corroborated these observations. |
| doi_str_mv | 10.1038/mt.2008.76 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_70759396</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><els_id>S1525001616317324</els_id><sourcerecordid>4073037511</sourcerecordid><originalsourceid>FETCH-LOGICAL-c501t-b7c7a17c6c6aee4c070dded0fb8e60758c850a0e4128d1b9e074421f0e5258d23</originalsourceid><addsrcrecordid>eNptkMGKFDEQhoMo7rp68QEkIHgQZkz1pJP0sVnWdWEXD7t6DZmkGjJMd9pUZnFuvoNv6JOYYQYF8VT_4eOD-hh7DWIJYmU-jGXZCGGWWj1h59A27UKIRj79s0GdsRdEm7qg7dRzdgZGgpRanTPsJ7fdUySeBt73X_k95lT2MxKHXz9-dvwOQ3QFA7_GCfnV9zkjUUwTd1PgDznNkUYeJ34XPfJ-KJj5_Z4KjtHzm2mDvlT4JXs2uC3hq9O9YF8-Xj1cflrcfr6-uexvF74VUBZr7bUD7ZVXDlF6oUUIGMSwNqiEbo03rXACJTQmwLpDoaVsYBBYHzWhWV2wd0fvnNO3HVKxYySP262bMO3I6irpVp2q4Nt_wE3a5ZqCLOiuUQArc9C9P1I-J6KMg51zHF3eWxD2kN6OxR7SW31Qvjkpd-sRw1_01LoC8ghgLfAYMVvyESdfA-eayYYU_-f9DcpRkAc</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1792611382</pqid></control><display><type>article</type><title>Analysis of AAV Serotypes 1–9 Mediated Gene Expression and Tropism in Mice After Systemic Injection</title><source>MEDLINE</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>Alma/SFX Local Collection</source><creator>Zincarelli, Carmela ; Soltys, Stephen ; Rengo, Giuseppe ; Rabinowitz, Joseph E</creator><creatorcontrib>Zincarelli, Carmela ; Soltys, Stephen ; Rengo, Giuseppe ; Rabinowitz, Joseph E</creatorcontrib><description>This study examines transgene expression and biodistribution of adeno-associated virus (AAV) pseudotyped 1–9 after tail vein (TV) injection in male mice. Using a cytomegalovirus (CMV)-luciferase transgene, the time-course of expression in each animal was tracked throughout the experiment. The animals were imaged at 7, 14, 29, 56, and 100 days after the TV injection. The total number of photons emitted from each animal was recorded, allowing examination of expression level and kinetics for each pseudotyped virus. The bioluminescence imaging revealed three expression levels (i) low-expression group, AAV2, 3, 4, and 5; (ii) moderate-expression group, AAV1, 6, and 8; and (iii) high-expression group, AAV7 and 9. In addition, imaging revealed two classes of kinetics (i) rapid-onset, for AAV1, 6, 7, 8, and 9; and (ii) slow-onset, for AAV2, 3, 4, and 5. We next evaluated protein expression and viral genome copy numbers in dissected tissues. AAV9 had the best viral genome distribution and highest protein levels. The AAV7 protein and genome copy numbers were comparable to those of AAV9 in the liver. Most surprisingly, AAV4 showed the greatest number of genome copies in lung and kidney, and a high copy number in the heart. AAV6 expression was observed in the heart, liver, and skeletal muscle, and the genome distribution corroborated these observations.</description><identifier>ISSN: 1525-0016</identifier><identifier>EISSN: 1525-0024</identifier><identifier>DOI: 10.1038/mt.2008.76</identifier><identifier>PMID: 18414476</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Animals ; Cytomegalovirus ; Dependovirus - genetics ; Dependovirus - metabolism ; Echocardiography - methods ; Gene expression ; Gene Expression Regulation ; Gene therapy ; Gene Transfer Techniques ; Genetic Therapy - methods ; Genome ; Genomes ; HeLa Cells ; Humans ; Kinetics ; Liver ; Male ; Medicine ; Mice ; Models, Genetic ; Musculoskeletal system ; Proteins ; Time Factors ; Transgenes</subject><ispartof>Molecular therapy, 2008-06, Vol.16 (6), p.1073-1080</ispartof><rights>2008 The American Society of Gene Therapy</rights><rights>Copyright Nature Publishing Group Jun 2008</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c501t-b7c7a17c6c6aee4c070dded0fb8e60758c850a0e4128d1b9e074421f0e5258d23</citedby><cites>FETCH-LOGICAL-c501t-b7c7a17c6c6aee4c070dded0fb8e60758c850a0e4128d1b9e074421f0e5258d23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18414476$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zincarelli, Carmela</creatorcontrib><creatorcontrib>Soltys, Stephen</creatorcontrib><creatorcontrib>Rengo, Giuseppe</creatorcontrib><creatorcontrib>Rabinowitz, Joseph E</creatorcontrib><title>Analysis of AAV Serotypes 1–9 Mediated Gene Expression and Tropism in Mice After Systemic Injection</title><title>Molecular therapy</title><addtitle>Mol Ther</addtitle><description>This study examines transgene expression and biodistribution of adeno-associated virus (AAV) pseudotyped 1–9 after tail vein (TV) injection in male mice. Using a cytomegalovirus (CMV)-luciferase transgene, the time-course of expression in each animal was tracked throughout the experiment. The animals were imaged at 7, 14, 29, 56, and 100 days after the TV injection. The total number of photons emitted from each animal was recorded, allowing examination of expression level and kinetics for each pseudotyped virus. The bioluminescence imaging revealed three expression levels (i) low-expression group, AAV2, 3, 4, and 5; (ii) moderate-expression group, AAV1, 6, and 8; and (iii) high-expression group, AAV7 and 9. In addition, imaging revealed two classes of kinetics (i) rapid-onset, for AAV1, 6, 7, 8, and 9; and (ii) slow-onset, for AAV2, 3, 4, and 5. We next evaluated protein expression and viral genome copy numbers in dissected tissues. AAV9 had the best viral genome distribution and highest protein levels. The AAV7 protein and genome copy numbers were comparable to those of AAV9 in the liver. Most surprisingly, AAV4 showed the greatest number of genome copies in lung and kidney, and a high copy number in the heart. AAV6 expression was observed in the heart, liver, and skeletal muscle, and the genome distribution corroborated these observations.</description><subject>Animals</subject><subject>Cytomegalovirus</subject><subject>Dependovirus - genetics</subject><subject>Dependovirus - metabolism</subject><subject>Echocardiography - methods</subject><subject>Gene expression</subject><subject>Gene Expression Regulation</subject><subject>Gene therapy</subject><subject>Gene Transfer Techniques</subject><subject>Genetic Therapy - methods</subject><subject>Genome</subject><subject>Genomes</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Kinetics</subject><subject>Liver</subject><subject>Male</subject><subject>Medicine</subject><subject>Mice</subject><subject>Models, Genetic</subject><subject>Musculoskeletal system</subject><subject>Proteins</subject><subject>Time Factors</subject><subject>Transgenes</subject><issn>1525-0016</issn><issn>1525-0024</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptkMGKFDEQhoMo7rp68QEkIHgQZkz1pJP0sVnWdWEXD7t6DZmkGjJMd9pUZnFuvoNv6JOYYQYF8VT_4eOD-hh7DWIJYmU-jGXZCGGWWj1h59A27UKIRj79s0GdsRdEm7qg7dRzdgZGgpRanTPsJ7fdUySeBt73X_k95lT2MxKHXz9-dvwOQ3QFA7_GCfnV9zkjUUwTd1PgDznNkUYeJ34XPfJ-KJj5_Z4KjtHzm2mDvlT4JXs2uC3hq9O9YF8-Xj1cflrcfr6-uexvF74VUBZr7bUD7ZVXDlF6oUUIGMSwNqiEbo03rXACJTQmwLpDoaVsYBBYHzWhWV2wd0fvnNO3HVKxYySP262bMO3I6irpVp2q4Nt_wE3a5ZqCLOiuUQArc9C9P1I-J6KMg51zHF3eWxD2kN6OxR7SW31Qvjkpd-sRw1_01LoC8ghgLfAYMVvyESdfA-eayYYU_-f9DcpRkAc</recordid><startdate>20080601</startdate><enddate>20080601</enddate><creator>Zincarelli, Carmela</creator><creator>Soltys, Stephen</creator><creator>Rengo, Giuseppe</creator><creator>Rabinowitz, Joseph E</creator><general>Elsevier Inc</general><general>Elsevier Limited</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M7P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20080601</creationdate><title>Analysis of AAV Serotypes 1–9 Mediated Gene Expression and Tropism in Mice After Systemic Injection</title><author>Zincarelli, Carmela ; Soltys, Stephen ; Rengo, Giuseppe ; Rabinowitz, Joseph E</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c501t-b7c7a17c6c6aee4c070dded0fb8e60758c850a0e4128d1b9e074421f0e5258d23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Animals</topic><topic>Cytomegalovirus</topic><topic>Dependovirus - genetics</topic><topic>Dependovirus - metabolism</topic><topic>Echocardiography - methods</topic><topic>Gene expression</topic><topic>Gene Expression Regulation</topic><topic>Gene therapy</topic><topic>Gene Transfer Techniques</topic><topic>Genetic Therapy - methods</topic><topic>Genome</topic><topic>Genomes</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Kinetics</topic><topic>Liver</topic><topic>Male</topic><topic>Medicine</topic><topic>Mice</topic><topic>Models, Genetic</topic><topic>Musculoskeletal system</topic><topic>Proteins</topic><topic>Time Factors</topic><topic>Transgenes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zincarelli, Carmela</creatorcontrib><creatorcontrib>Soltys, Stephen</creatorcontrib><creatorcontrib>Rengo, Giuseppe</creatorcontrib><creatorcontrib>Rabinowitz, Joseph E</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>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</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>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>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</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>Biological Science Database</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>MEDLINE - Academic</collection><jtitle>Molecular therapy</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zincarelli, Carmela</au><au>Soltys, Stephen</au><au>Rengo, Giuseppe</au><au>Rabinowitz, Joseph E</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Analysis of AAV Serotypes 1–9 Mediated Gene Expression and Tropism in Mice After Systemic Injection</atitle><jtitle>Molecular therapy</jtitle><addtitle>Mol Ther</addtitle><date>2008-06-01</date><risdate>2008</risdate><volume>16</volume><issue>6</issue><spage>1073</spage><epage>1080</epage><pages>1073-1080</pages><issn>1525-0016</issn><eissn>1525-0024</eissn><abstract>This study examines transgene expression and biodistribution of adeno-associated virus (AAV) pseudotyped 1–9 after tail vein (TV) injection in male mice. Using a cytomegalovirus (CMV)-luciferase transgene, the time-course of expression in each animal was tracked throughout the experiment. The animals were imaged at 7, 14, 29, 56, and 100 days after the TV injection. The total number of photons emitted from each animal was recorded, allowing examination of expression level and kinetics for each pseudotyped virus. The bioluminescence imaging revealed three expression levels (i) low-expression group, AAV2, 3, 4, and 5; (ii) moderate-expression group, AAV1, 6, and 8; and (iii) high-expression group, AAV7 and 9. In addition, imaging revealed two classes of kinetics (i) rapid-onset, for AAV1, 6, 7, 8, and 9; and (ii) slow-onset, for AAV2, 3, 4, and 5. We next evaluated protein expression and viral genome copy numbers in dissected tissues. AAV9 had the best viral genome distribution and highest protein levels. The AAV7 protein and genome copy numbers were comparable to those of AAV9 in the liver. Most surprisingly, AAV4 showed the greatest number of genome copies in lung and kidney, and a high copy number in the heart. AAV6 expression was observed in the heart, liver, and skeletal muscle, and the genome distribution corroborated these observations.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>18414476</pmid><doi>10.1038/mt.2008.76</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1525-0016 |
| ispartof | Molecular therapy, 2008-06, Vol.16 (6), p.1073-1080 |
| issn | 1525-0016 1525-0024 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70759396 |
| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Animals Cytomegalovirus Dependovirus - genetics Dependovirus - metabolism Echocardiography - methods Gene expression Gene Expression Regulation Gene therapy Gene Transfer Techniques Genetic Therapy - methods Genome Genomes HeLa Cells Humans Kinetics Liver Male Medicine Mice Models, Genetic Musculoskeletal system Proteins Time Factors Transgenes |
| title | Analysis of AAV Serotypes 1–9 Mediated Gene Expression and Tropism in Mice After Systemic Injection |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-31T06%3A07%3A35IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_cross&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Analysis%20of%20AAV%20Serotypes%201%E2%80%939%20Mediated%20Gene%20Expression%20and%20Tropism%20in%20Mice%20After%20Systemic%20Injection&rft.jtitle=Molecular%20therapy&rft.au=Zincarelli,%20Carmela&rft.date=2008-06-01&rft.volume=16&rft.issue=6&rft.spage=1073&rft.epage=1080&rft.pages=1073-1080&rft.issn=1525-0016&rft.eissn=1525-0024&rft_id=info:doi/10.1038/mt.2008.76&rft_dat=%3Cproquest_cross%3E4073037511%3C/proquest_cross%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1792611382&rft_id=info:pmid/18414476&rft_els_id=S1525001616317324&rfr_iscdi=true |