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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
2007-2-2
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pubmed:abstractText |
We have previously demonstrated that hybrid adeno-associated viral (AAV) vectors bearing nonhomologous inverted terminal repeats (ITRs) enhance directional intermolecular recombination and the efficiency of dual-AAV vector trans-splicing in cultured cells. Using hybrid-ITR vectors carrying two exons of a lacZ minigene, we demonstrate that this dual-vector approach also mediates higher levels (3- to 6-fold) of gene reconstitution in mouse skeletal muscle, liver, and heart. Inhibition of the proteasome by systemic administration of Doxil (Food and Drug Administration-approved lipid-formulated doxorubicin) further enhanced dual-vector trans-splicing 6- to 12-fold in two mouse strains. Hence, using hybrid-ITR AAV vectors in combination with proteasome modulation enhanced dual-vector delivery of a transgene approximately 36-fold over the current dual-vector trans-splicing approaches. These data provide in vivo evidence that ITR sequence-dependent homologous recombination, rather than nonhomologous end joining, is the predominant mechanism for AAV genome heterodimerization. Hence, enhanced directional recombination provided by hybrid-ITR vectors may be a useful in vivo strategy for improving dual-vector delivery of transgenes larger than the AAV packaging limit.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-10516055,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-10802620,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-10802719,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-10802720,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-10841516,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-10841568,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-10941572,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-11273783,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-11592843,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-11883078,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-12573057,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-12573623,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-12596997,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-12663782,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-12805434,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-14990705,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-15596830,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-15668136,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-16244658,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-16352567,
http://linkedlifedata.com/resource/pubmed/commentcorrection/17181493-16899463
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
1043-0342
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
18
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
81-7
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pubmed:dateRevised |
2011-4-27
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pubmed:meshHeading |
pubmed-meshheading:17181493-Animals,
pubmed-meshheading:17181493-Antibiotics, Antineoplastic,
pubmed-meshheading:17181493-Cell Line,
pubmed-meshheading:17181493-Dependovirus,
pubmed-meshheading:17181493-Doxorubicin,
pubmed-meshheading:17181493-Gene Expression Regulation, Viral,
pubmed-meshheading:17181493-Genetic Vectors,
pubmed-meshheading:17181493-Genome, Viral,
pubmed-meshheading:17181493-Lac Operon,
pubmed-meshheading:17181493-Mice,
pubmed-meshheading:17181493-Terminal Repeat Sequences,
pubmed-meshheading:17181493-Trans-Splicing,
pubmed-meshheading:17181493-Transduction, Genetic,
pubmed-meshheading:17181493-Transgenes
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pubmed:year |
2007
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pubmed:articleTitle |
Hybrid adeno-associated virus bearing nonhomologous inverted terminal repeats enhances dual-vector reconstruction of minigenes in vivo.
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pubmed:affiliation |
Department of Anatomy and Cell Biology, University of Iowa School of Medicine, Iowa City, IA 52242, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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