Source:http://linkedlifedata.com/resource/pubmed/id/10985957
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions |
umls-concept:C0007600,
umls-concept:C0030176,
umls-concept:C0033268,
umls-concept:C0035366,
umls-concept:C0036043,
umls-concept:C0079411,
umls-concept:C0086022,
umls-concept:C0184511,
umls-concept:C0185125,
umls-concept:C0205210,
umls-concept:C0442335,
umls-concept:C0475208,
umls-concept:C1705099,
umls-concept:C1709696
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| pubmed:issue |
3
|
| pubmed:dateCreated |
2000-10-13
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| pubmed:abstractText |
For many applications, human clinical therapies using retroviral vectors still require many technological improvements in key areas of vector design and production. These improvements include higher unprocessed manufacturing titers, complement-resistant vectors, and minimized potential to generate replication-competent retrovirus (RCR). To address these issues, we have developed a panel of human packaging cell lines (PCLs) with reduced homology between retroviral vector and packaging components. These reduced-homology PCLs allowed for the use of a novel high multiplicity of transduction ("high m.o. t.") method to introduce multiple copies of provector within vector-producing cell lines (VPCLs), resulting in high-titer vector without the generation of RCR. In a distinct approach to increase vector yields, we integrated manufacturing parameters into screening strategies and clone selection for large-scale vector production. Collectively, these improvements have resulted in the development of diverse VPCLs with unprocessed titers exceeding 2 x 10(7) CFU/ml. Using this technology, human Factor VIII VPCLs yielding titers as high as 2 x 10(8) CFU/ml unprocessed supernatant were generated. These cell lines produce complement-resistant vector particles (N. J. DePolo et al., J. Virol. 73: 6708-6714, 1999) and provide the basis for an ongoing Factor VIII gene therapy clinical trial.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
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| pubmed:month |
Sep
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| pubmed:issn |
1525-0016
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| pubmed:author |
pubmed-author:BodnerMM,
pubmed-author:ChangS MSM,
pubmed-author:DePoloN JNJ,
pubmed-author:DriverD ADA,
pubmed-author:DubenskyT WTWJr,
pubmed-author:GreengardJ SJS,
pubmed-author:IbañezC ECE,
pubmed-author:JollyD JDJ,
pubmed-author:LynnAA,
pubmed-author:McCormackJ EJE,
pubmed-author:MooreM DMD,
pubmed-author:NguyenKK,
pubmed-author:O'DeaJJ,
pubmed-author:PhuongT KTK,
pubmed-author:RespessJJ,
pubmed-author:SajjadiN CNC,
pubmed-author:SauterS LSL,
pubmed-author:SheridanP LPL,
pubmed-author:TownsendKK,
pubmed-author:de la VegaD JDJJr
|
| pubmed:issnType |
Print
|
| pubmed:volume |
2
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
262-75
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| pubmed:dateRevised |
2006-4-21
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| pubmed:meshHeading |
pubmed-meshheading:10985957-Base Sequence,
pubmed-meshheading:10985957-Cell Line,
pubmed-meshheading:10985957-DNA Primers,
pubmed-meshheading:10985957-Factor VIII,
pubmed-meshheading:10985957-Genetic Vectors,
pubmed-meshheading:10985957-Hemophilia A,
pubmed-meshheading:10985957-Humans,
pubmed-meshheading:10985957-Retroviridae,
pubmed-meshheading:10985957-Virus Assembly
|
| pubmed:year |
2000
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| pubmed:articleTitle |
Generation of retroviral packaging and producer cell lines for large-scale vector production and clinical application: improved safety and high titer.
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| pubmed:affiliation |
Chiron Corporation, Center for Gene Therapy, San Diego, California 92121, USA.
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| pubmed:publicationType |
Journal Article
|