Approaches to improving the kinetics of adenovirus-delivered genes and gene products

Adenovirus (Ad) vectors have been expected to play a great role in gene therapy because of their extremely high transduction efficiency and wide tropism. However, due to the intrinsic deficiency of their immunogenic toxicities, Ad vectors are rapidly cleared from the host, transgene expression is tr...

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Bibliographic Details
Published in:Advanced drug delivery reviews 2005-04, Vol.57 (5), p.781-802
Main Authors: Xu, Zhi-Li, Mizuguchi, Hiroyuki, Sakurai, Fuminori, Koizumi, Naoya, Hosono, Tetsuji, Kawabata, Kenji, Watanabe, Yoshiteru, Yamaguchi, Teruhide, Hayakawa, Takao
Format: Article
Language:English
Subjects:
Adenoviridae - genetics
Animals
Biodistribution
Cationic liposome
Drug Delivery Systems - methods
Genetic Therapy - methods
Genetic Vectors - administration & dosage
Genetic Vectors - chemical synthesis
Genetic Vectors - pharmacokinetics
Helper-dependent
Humans
Immunogenic toxicities
In-cis acting element
Integration
PEGylation
Regulatable expression
Targeting
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Summary:Adenovirus (Ad) vectors have been expected to play a great role in gene therapy because of their extremely high transduction efficiency and wide tropism. However, due to the intrinsic deficiency of their immunogenic toxicities, Ad vectors are rapidly cleared from the host, transgene expression is transient, and readministration of the same serotype Ad vectors is problematic. As a result, Ad vectors are continually undergoing refinement to realize their potential for gene therapy application. Even after 1999, when a patient fatally succumbed to the toxicity associated with Ad vector administration at a University of Pennsylvania (U.S.) experimental clinic, enthusiasm of gene therapists for Ad vectors has not waned. With great efforts from various research groups, significant advances have been achieved through comprehensive approaches to improving the kinetics of Ad vector-delivered genes and gene products.
ISSN:0169-409X
1872-8294
DOI:10.1016/j.addr.2004.12.010