A sensitive noninvasive method for monitoring successful liver-directed gene transfer of the low-density lipoprotein receptor in Watanabe hyperlipidemic rabbits in vivo.
Identifieur interne : 003142 ( Main/Exploration ); précédent : 003141; suivant : 003143A sensitive noninvasive method for monitoring successful liver-directed gene transfer of the low-density lipoprotein receptor in Watanabe hyperlipidemic rabbits in vivo.
Auteurs : RBID : pubmed:14724675English descriptors
- KwdEn :
- Adenoviridae (genetics), Animals, Female, Gene Expression, Genetic Therapy (methods), Genetic Vectors (administration & dosage), Hyperlipoproteinemias (metabolism), Hyperlipoproteinemias (therapy), Indium Radioisotopes (diagnostic use), Injections, Intravenous, Lipoproteins, LDL (administration & dosage), Lipoproteins, LDL (pharmacokinetics), Liver (metabolism), Liver (radionuclide imaging), Rabbits, Receptors, LDL (genetics), Receptors, LDL (metabolism), Transduction, Genetic (methods), Transgenes, Treatment Outcome.
- MESH :
- chemical , administration & dosage : Lipoproteins, LDL.
- chemical , diagnostic use : Indium Radioisotopes.
- administration & dosage : Genetic Vectors.
- genetics : Adenoviridae, Receptors, LDL.
- metabolism : Hyperlipoproteinemias, Liver, Receptors, LDL.
- methods : Genetic Therapy, Transduction, Genetic.
- chemical , pharmacokinetics : Lipoproteins, LDL.
- radionuclide imaging : Liver.
- therapy : Hyperlipoproteinemias.
- Animals, Female, Gene Expression, Injections, Intravenous, Rabbits, Transgenes, Treatment Outcome.
Abstract
Noninvasive tools to quantitate transgene expression directly are a prerequisite for clinical gene therapy. We established a method to determine location, magnitude, and duration of low-density lipoprotein (LDL) receptor (LDLR) transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe hypercholesterolemic rabbits by following tissue uptake of intravenously injected (111)In-labeled LDL using a scintillation camera. Liver-specific tracer uptake was calculated by normalizing the counts measured over the liver to counts measured over the heart that represent the circulating blood pool of the tracer (liver/heart (L/H) ratio). Our results indicate that the optimal time point for transgene imaging is 4 h after the tracer injection. Compared with control virus-injected rabbits, animals treated with the LDLR-expressing adenovirus showed seven-fold higher L/H ratios on day 6 after gene transfer, and had still 4.5-fold higher L/H ratios on day 30. This imaging method might be a useful strategy to obtain reliable data on functional transgene expression in clinical gene therapy trials of familial hypercholesterolemia.
DOI: 10.1038/sj.gt.3302206
PubMed: 14724675
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Le document en format XML
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<author><name sortKey="Tietge, U J F" uniqKey="Tietge U">U J F Tietge</name>
<affiliation wicri:level="3"><nlm:affiliation>Department of Medicine and NWFZ, Charité Campus Mitte, Humboldt University, Berlin, Germany.</nlm:affiliation>
<country xml:lang="fr">Allemagne</country>
<wicri:regionArea>Department of Medicine and NWFZ, Charité Campus Mitte, Humboldt University, Berlin</wicri:regionArea>
<placeName><region type="land" nuts="3">Berlin</region>
<settlement type="city">Berlin</settlement>
</placeName>
</affiliation>
</author>
<author><name sortKey="Cichon, G" uniqKey="Cichon G">G Cichon</name>
</author>
<author><name sortKey="B Ttner, C" uniqKey="B Ttner C">C Büttner</name>
</author>
<author><name sortKey="Genschel, J" uniqKey="Genschel J">J Genschel</name>
</author>
<author><name sortKey="Heeren, J" uniqKey="Heeren J">J Heeren</name>
</author>
<author><name sortKey="Gielow, P" uniqKey="Gielow P">P Gielow</name>
</author>
<author><name sortKey="Grewe, N" uniqKey="Grewe N">N Grewe</name>
</author>
<author><name sortKey="Dogar, M" uniqKey="Dogar M">M Dogar</name>
</author>
<author><name sortKey="Beisiegel, U" uniqKey="Beisiegel U">U Beisiegel</name>
</author>
<author><name sortKey="Manns, M P" uniqKey="Manns M">M P Manns</name>
</author>
<author><name sortKey="Lochs, H" uniqKey="Lochs H">H Lochs</name>
</author>
<author><name sortKey="Burchert, W" uniqKey="Burchert W">W Burchert</name>
</author>
<author><name sortKey="Schmidt, H H J" uniqKey="Schmidt H">H H-J Schmidt</name>
</author>
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<publicationStmt><date when="2004">2004</date>
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<idno type="doi">10.1038/sj.gt.3302206</idno>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenoviridae (genetics)</term>
<term>Animals</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Genetic Therapy (methods)</term>
<term>Genetic Vectors (administration & dosage)</term>
<term>Hyperlipoproteinemias (metabolism)</term>
<term>Hyperlipoproteinemias (therapy)</term>
<term>Indium Radioisotopes (diagnostic use)</term>
<term>Injections, Intravenous</term>
<term>Lipoproteins, LDL (administration & dosage)</term>
<term>Lipoproteins, LDL (pharmacokinetics)</term>
<term>Liver (metabolism)</term>
<term>Liver (radionuclide imaging)</term>
<term>Rabbits</term>
<term>Receptors, LDL (genetics)</term>
<term>Receptors, LDL (metabolism)</term>
<term>Transduction, Genetic (methods)</term>
<term>Transgenes</term>
<term>Treatment Outcome</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Lipoproteins, LDL</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="diagnostic use" xml:lang="en"><term>Indium Radioisotopes</term>
</keywords>
<keywords scheme="MESH" qualifier="administration & dosage" xml:lang="en"><term>Genetic Vectors</term>
</keywords>
<keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Adenoviridae</term>
<term>Receptors, LDL</term>
</keywords>
<keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Hyperlipoproteinemias</term>
<term>Liver</term>
<term>Receptors, LDL</term>
</keywords>
<keywords scheme="MESH" qualifier="methods" xml:lang="en"><term>Genetic Therapy</term>
<term>Transduction, Genetic</term>
</keywords>
<keywords scheme="MESH" type="chemical" qualifier="pharmacokinetics" xml:lang="en"><term>Lipoproteins, LDL</term>
</keywords>
<keywords scheme="MESH" qualifier="radionuclide imaging" xml:lang="en"><term>Liver</term>
</keywords>
<keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Hyperlipoproteinemias</term>
</keywords>
<keywords scheme="MESH" xml:lang="en"><term>Animals</term>
<term>Female</term>
<term>Gene Expression</term>
<term>Injections, Intravenous</term>
<term>Rabbits</term>
<term>Transgenes</term>
<term>Treatment Outcome</term>
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<front><div type="abstract" xml:lang="en">Noninvasive tools to quantitate transgene expression directly are a prerequisite for clinical gene therapy. We established a method to determine location, magnitude, and duration of low-density lipoprotein (LDL) receptor (LDLR) transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe hypercholesterolemic rabbits by following tissue uptake of intravenously injected (111)In-labeled LDL using a scintillation camera. Liver-specific tracer uptake was calculated by normalizing the counts measured over the liver to counts measured over the heart that represent the circulating blood pool of the tracer (liver/heart (L/H) ratio). Our results indicate that the optimal time point for transgene imaging is 4 h after the tracer injection. Compared with control virus-injected rabbits, animals treated with the LDLR-expressing adenovirus showed seven-fold higher L/H ratios on day 6 after gene transfer, and had still 4.5-fold higher L/H ratios on day 30. This imaging method might be a useful strategy to obtain reliable data on functional transgene expression in clinical gene therapy trials of familial hypercholesterolemia.</div>
</front>
</TEI>
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<DateCreated><Year>2004</Year>
<Month>03</Month>
<Day>18</Day>
</DateCreated>
<DateCompleted><Year>2004</Year>
<Month>07</Month>
<Day>21</Day>
</DateCompleted>
<DateRevised><Year>2012</Year>
<Month>11</Month>
<Day>15</Day>
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<Article PubModel="Print"><Journal><ISSN IssnType="Print">0969-7128</ISSN>
<JournalIssue CitedMedium="Print"><Volume>11</Volume>
<Issue>7</Issue>
<PubDate><Year>2004</Year>
<Month>Apr</Month>
</PubDate>
</JournalIssue>
<Title>Gene therapy</Title>
<ISOAbbreviation>Gene Ther.</ISOAbbreviation>
</Journal>
<ArticleTitle>A sensitive noninvasive method for monitoring successful liver-directed gene transfer of the low-density lipoprotein receptor in Watanabe hyperlipidemic rabbits in vivo.</ArticleTitle>
<Pagination><MedlinePgn>574-80</MedlinePgn>
</Pagination>
<Abstract><AbstractText>Noninvasive tools to quantitate transgene expression directly are a prerequisite for clinical gene therapy. We established a method to determine location, magnitude, and duration of low-density lipoprotein (LDL) receptor (LDLR) transgene expression after adenoviral gene transfer into LDLR-deficient Watanabe hypercholesterolemic rabbits by following tissue uptake of intravenously injected (111)In-labeled LDL using a scintillation camera. Liver-specific tracer uptake was calculated by normalizing the counts measured over the liver to counts measured over the heart that represent the circulating blood pool of the tracer (liver/heart (L/H) ratio). Our results indicate that the optimal time point for transgene imaging is 4 h after the tracer injection. Compared with control virus-injected rabbits, animals treated with the LDLR-expressing adenovirus showed seven-fold higher L/H ratios on day 6 after gene transfer, and had still 4.5-fold higher L/H ratios on day 30. This imaging method might be a useful strategy to obtain reliable data on functional transgene expression in clinical gene therapy trials of familial hypercholesterolemia.</AbstractText>
</Abstract>
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<ForeName>U J F</ForeName>
<Initials>UJ</Initials>
<Affiliation>Department of Medicine and NWFZ, Charité Campus Mitte, Humboldt University, Berlin, Germany.</Affiliation>
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<Author ValidYN="Y"><LastName>Cichon</LastName>
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<Author ValidYN="Y"><LastName>Büttner</LastName>
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<MeshHeading><DescriptorName MajorTopicYN="N">Transgenes</DescriptorName>
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<MeshHeading><DescriptorName MajorTopicYN="N">Treatment Outcome</DescriptorName>
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