Transduction of Nonhuman Primate Brain with Adeno-Associated Virus Serotype 1 : Vector Trafficking and Immune Response
Identifieur interne : 001566 ( Main/Exploration ); précédent : 001565; suivant : 001567Transduction of Nonhuman Primate Brain with Adeno-Associated Virus Serotype 1 : Vector Trafficking and Immune Response
Auteurs : Piotr Hadaczek [États-Unis] ; John Forsayeth [États-Unis] ; Hanna Mirek [États-Unis] ; Keith Munson [États-Unis] ; John Bringas [États-Unis] ; Phil Pivirotto [États-Unis] ; Jodi L. Mcbride [États-Unis] ; Beverly L. Davidson [États-Unis] ; Krystof S. Bankiewicz [États-Unis]Source :
- Human gene therapy [ 1043-0342 ] ; 2009.
Descripteurs français
- Pascal (Inist)
English descriptors
- KwdEn :
Abstract
We used convection-enhanced delivery (CED) to characterize gene delivery mediated by adeno-associated virus type 1 (AAV1) by tracking expression of hrGFP (humanized green fluorescent protein from Renilla reniformis) into the striatum, basal forebrain, and corona radiata of monkey brain. Four cynomolgus monkeys received single infusions into corona radiata, putamen, and caudate. The other group (n = 4) received infusions into basal forebrain. Thirty days after infusion animals were killed and their brains were processed for immunohistochemical evaluation. Volumetric analysis of GFP-positive brain areas was performed. AAV1-hrGFP infusions resulted in approximately 550, 700, and 73 mm3 coverage after infusion into corona radiata, striatum, and basal forebrain, respectively. Aside from targeted regions, other brain structures also showed GFP signal (internal and external globus pallidus, subthalamic nucleus), supporting the idea that AAV1 is actively trafficked to regions distal from the infusion site. In addition to neuronal transduction, a significant nonneuronal cell population was transduced by AAV1 vector; for example, oligodendrocytes in corona radiata and astrocytes in the striatum. We observed a strong humoral and cell-mediated response against AAV1-hrGFP in transduced monkeys irrespective of the anatomic location of the infusion, as evidenced by induction of circulating anti-AAV1 and anti-hrGFP antibodies, as well as infiltration of CD4+ lymphocytes and upregulation of MHC-II in regions infused with vector. We conclude that transduction of antigen-presenting cells within the CNS is a likely cause of this response and that caution is warranted when foreign transgenes are used as reporters in gene therapy studies with vectors with broader tropism than AAV2.
Affiliations:
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<record><TEI><teiHeader><fileDesc><titleStmt><title xml:lang="en" level="a">Transduction of Nonhuman Primate Brain with Adeno-Associated Virus Serotype 1 : Vector Trafficking and Immune Response</title><author><name sortKey="Hadaczek, Piotr" sort="Hadaczek, Piotr" uniqKey="Hadaczek P" first="Piotr" last="Hadaczek">Piotr Hadaczek</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Forsayeth, John" sort="Forsayeth, John" uniqKey="Forsayeth J" first="John" last="Forsayeth">John Forsayeth</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Mirek, Hanna" sort="Mirek, Hanna" uniqKey="Mirek H" first="Hanna" last="Mirek">Hanna Mirek</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Munson, Keith" sort="Munson, Keith" uniqKey="Munson K" first="Keith" last="Munson">Keith Munson</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Targeted Genetics</s1><s2>Seattle, WA 98101</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Bringas, John" sort="Bringas, John" uniqKey="Bringas J" first="John" last="Bringas">John Bringas</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Pivirotto, Phil" sort="Pivirotto, Phil" uniqKey="Pivirotto P" first="Phil" last="Pivirotto">Phil Pivirotto</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Mcbride, Jodi L" sort="Mcbride, Jodi L" uniqKey="Mcbride J" first="Jodi L." last="Mcbride">Jodi L. Mcbride</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Internal Medicine, University of Iowa</s1><s2>Iowa City, IA 52242</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Davidson, Beverly L" sort="Davidson, Beverly L" uniqKey="Davidson B" first="Beverly L." last="Davidson">Beverly L. Davidson</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Internal Medicine, University of Iowa</s1><s2>Iowa City, IA 52242</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Bankiewicz, Krystof S" sort="Bankiewicz, Krystof S" uniqKey="Bankiewicz K" first="Krystof S." last="Bankiewicz">Krystof S. Bankiewicz</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">INIST</idno><idno type="inist">09-0180512</idno><date when="2009">2009</date><idno type="stanalyst">PASCAL 09-0180512 INIST</idno><idno type="RBID">Pascal:09-0180512</idno><idno type="wicri:Area/PascalFrancis/Corpus">000026</idno><idno type="wicri:Area/PascalFrancis/Curation">000033</idno><idno type="wicri:Area/PascalFrancis/Checkpoint">000020</idno><idno type="wicri:explorRef" wicri:stream="PascalFrancis" wicri:step="Checkpoint">000020</idno><idno type="wicri:doubleKey">1043-0342:2009:Hadaczek P:transduction:of:nonhuman</idno><idno type="wicri:Area/Main/Merge">001568</idno><idno type="wicri:Area/Main/Curation">001566</idno><idno type="wicri:Area/Main/Exploration">001566</idno></publicationStmt><sourceDesc><biblStruct><analytic><title xml:lang="en" level="a">Transduction of Nonhuman Primate Brain with Adeno-Associated Virus Serotype 1 : Vector Trafficking and Immune Response</title><author><name sortKey="Hadaczek, Piotr" sort="Hadaczek, Piotr" uniqKey="Hadaczek P" first="Piotr" last="Hadaczek">Piotr Hadaczek</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Forsayeth, John" sort="Forsayeth, John" uniqKey="Forsayeth J" first="John" last="Forsayeth">John Forsayeth</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Mirek, Hanna" sort="Mirek, Hanna" uniqKey="Mirek H" first="Hanna" last="Mirek">Hanna Mirek</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Munson, Keith" sort="Munson, Keith" uniqKey="Munson K" first="Keith" last="Munson">Keith Munson</name><affiliation wicri:level="2"><inist:fA14 i1="02"><s1>Targeted Genetics</s1><s2>Seattle, WA 98101</s2><s3>USA</s3><sZ>4 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Washington (État)</region></placeName></affiliation></author><author><name sortKey="Bringas, John" sort="Bringas, John" uniqKey="Bringas J" first="John" last="Bringas">John Bringas</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Pivirotto, Phil" sort="Pivirotto, Phil" uniqKey="Pivirotto P" first="Phil" last="Pivirotto">Phil Pivirotto</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author><author><name sortKey="Mcbride, Jodi L" sort="Mcbride, Jodi L" uniqKey="Mcbride J" first="Jodi L." last="Mcbride">Jodi L. Mcbride</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Internal Medicine, University of Iowa</s1><s2>Iowa City, IA 52242</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Davidson, Beverly L" sort="Davidson, Beverly L" uniqKey="Davidson B" first="Beverly L." last="Davidson">Beverly L. Davidson</name><affiliation wicri:level="4"><inist:fA14 i1="03"><s1>Department of Internal Medicine, University of Iowa</s1><s2>Iowa City, IA 52242</s2><s3>USA</s3><sZ>7 aut.</sZ><sZ>8 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Iowa</region><settlement type="city">Iowa City</settlement></placeName><orgName type="university">Université de l'Iowa</orgName></affiliation></author><author><name sortKey="Bankiewicz, Krystof S" sort="Bankiewicz, Krystof S" uniqKey="Bankiewicz K" first="Krystof S." last="Bankiewicz">Krystof S. Bankiewicz</name><affiliation wicri:level="2"><inist:fA14 i1="01"><s1>Laboratory of Molecular Therapeutics, Department of Neurosurgery, University of California, San Francisco</s1><s2>San Francisco, CA 94103</s2><s3>USA</s3><sZ>1 aut.</sZ><sZ>2 aut.</sZ><sZ>3 aut.</sZ><sZ>5 aut.</sZ><sZ>6 aut.</sZ><sZ>9 aut.</sZ></inist:fA14><country>États-Unis</country><placeName><region type="state">Californie</region></placeName></affiliation></author></analytic><series><title level="j" type="main">Human gene therapy</title><title level="j" type="abbreviated">Hum. gene ther.</title><idno type="ISSN">1043-0342</idno><imprint><date when="2009">2009</date></imprint></series></biblStruct></sourceDesc><seriesStmt><title level="j" type="main">Human gene therapy</title><title level="j" type="abbreviated">Hum. gene ther.</title><idno type="ISSN">1043-0342</idno></seriesStmt></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Dependovirus</term><term>Encephalon</term><term>Gene therapy</term><term>Immune response</term><term>Primates</term><term>Serotype</term><term>Transduction</term><term>Vector</term></keywords><keywords scheme="Pascal" xml:lang="fr"><term>Transduction</term><term>Primates</term><term>Encéphale</term><term>Sérotype</term><term>Vecteur</term><term>Réponse immune</term><term>Thérapie génique</term><term>Dependovirus</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">We used convection-enhanced delivery (CED) to characterize gene delivery mediated by adeno-associated virus type 1 (AAV1) by tracking expression of hrGFP (humanized green fluorescent protein from Renilla reniformis) into the striatum, basal forebrain, and corona radiata of monkey brain. Four cynomolgus monkeys received single infusions into corona radiata, putamen, and caudate. The other group (n = 4) received infusions into basal forebrain. Thirty days after infusion animals were killed and their brains were processed for immunohistochemical evaluation. Volumetric analysis of GFP-positive brain areas was performed. AAV1-hrGFP infusions resulted in approximately 550, 700, and 73 mm<sup>3</sup> coverage after infusion into corona radiata, striatum, and basal forebrain, respectively. Aside from targeted regions, other brain structures also showed GFP signal (internal and external globus pallidus, subthalamic nucleus), supporting the idea that AAV1 is actively trafficked to regions distal from the infusion site. In addition to neuronal transduction, a significant nonneuronal cell population was transduced by AAV1 vector; for example, oligodendrocytes in corona radiata and astrocytes in the striatum. We observed a strong humoral and cell-mediated response against AAV1-hrGFP in transduced monkeys irrespective of the anatomic location of the infusion, as evidenced by induction of circulating anti-AAV1 and anti-hrGFP antibodies, as well as infiltration of CD4<sup>+</sup> lymphocytes and upregulation of MHC-II in regions infused with vector. We conclude that transduction of antigen-presenting cells within the CNS is a likely cause of this response and that caution is warranted when foreign transgenes are used as reporters in gene therapy studies with vectors with broader tropism than AAV2.</div></front></TEI><affiliations><list><country><li>États-Unis</li></country><region><li>Californie</li><li>Iowa</li><li>Washington (État)</li></region><settlement><li>Iowa City</li></settlement><orgName><li>Université de l'Iowa</li></orgName></list><tree><country name="États-Unis"><region name="Californie"><name sortKey="Hadaczek, Piotr" sort="Hadaczek, Piotr" uniqKey="Hadaczek P" first="Piotr" last="Hadaczek">Piotr Hadaczek</name></region><name sortKey="Bankiewicz, Krystof S" sort="Bankiewicz, Krystof S" uniqKey="Bankiewicz K" first="Krystof S." last="Bankiewicz">Krystof S. Bankiewicz</name><name sortKey="Bringas, John" sort="Bringas, John" uniqKey="Bringas J" first="John" last="Bringas">John Bringas</name><name sortKey="Davidson, Beverly L" sort="Davidson, Beverly L" uniqKey="Davidson B" first="Beverly L." last="Davidson">Beverly L. Davidson</name><name sortKey="Forsayeth, John" sort="Forsayeth, John" uniqKey="Forsayeth J" first="John" last="Forsayeth">John Forsayeth</name><name sortKey="Mcbride, Jodi L" sort="Mcbride, Jodi L" uniqKey="Mcbride J" first="Jodi L." last="Mcbride">Jodi L. Mcbride</name><name sortKey="Mirek, Hanna" sort="Mirek, Hanna" uniqKey="Mirek H" first="Hanna" last="Mirek">Hanna Mirek</name><name sortKey="Munson, Keith" sort="Munson, Keith" uniqKey="Munson K" first="Keith" last="Munson">Keith Munson</name><name sortKey="Pivirotto, Phil" sort="Pivirotto, Phil" uniqKey="Pivirotto P" first="Phil" last="Pivirotto">Phil Pivirotto</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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