Abstract:
:First-generation adenoviral (Ad) and high-capacity adenoviral (HC-Ad) vectors are efficient delivery vehicles for transferring therapeutic transgenes in vivo into tissues/organs. The initial successes reported with adenoviral vectors in preclinical trials have been limited by immune-related adverse side effects. This has been, in part, attributed to the use of poorly characterized preparations of adenoviral vectors and also to the untoward immune adverse side effects elicited when high doses of these vectors were used. HC-Ads have several advantages over Ads, including the lack of viral coding sequences, which after infection and uncoating, makes them invisible to the host's immune system. Another advantage is their large cloning capacity (up to approximately 35 kb). However, accurate characterization of HC-Ad vectors, and of contaminating replication-competent adenovirus (RCA) or helper virus, is necessary before these preparations can be used safely in clinical trials. Consequently, the development of accurate, simple, and reproducible methods to standardize and validate adenoviral preparations for the presence of contaminant genomes is required. By using a molecular method that allows accurate, reproducible, and simultaneous determination of HC-Ad, contaminating helper virus, and RCA genome copy numbers based on real-time quantitative PCR, we demonstrate accurate detection of these three genomic entities, within CsCl-purified vector stocks, total DNA isolated from cells transduced in vitro, and from brain tissue infected in vivo. This approach will allow accurate assessment of the levels and biodistribution of HC-Ad and improve the safety and efficacy of clinical trials.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Puntel M,Curtin JF,Zirger JM,Muhammad AK,Xiong W,Liu C,Hu J,Kroeger KM,Czer P,Sciascia S,Mondkar S,Lowenstein PR,Castro MGdoi
10.1089/hum.2006.17.531subject
Has Abstractpub_date
2006-05-01 00:00:00pages
531-44issue
5eissn
1043-0342issn
1557-7422journal_volume
17pub_type
杂志文章abstract::An E1-, E2a-, E3-deleted adenoviral vector (Av3H82) encoding an epitope-tagged B domain-deleted human factor VIII cDNA (flagged FVIII) was evaluated in nonhuman primates. Twelve cynomolgus monkeys received intravenous administration of Av3H82; 6 monkeys received 6 x 10(11) particles/kg and another 6 received 3 x 10(12...
journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.13-1595
更新日期:1996-08-20 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2013.191
更新日期:2014-11-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2020.005
更新日期:2021-01-22 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1994.5.12-1477
更新日期:1994-12-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1996.7.13-1491
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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pub_type: 杂志文章,评审
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pub_type: 杂志文章
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journal_title:Human gene therapy
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