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PMID: 11932426 Published · ppublish English Evaluation Study Journal Article

Exploiting the natural diversity in adenovirus tropism for therapy and prevention of disease.

Journal of virology ·Vol. 76 ·No. 9 ·2002-05-00 ·Pages 4612-20

Havenga MJ, Lemckert AA, Ophorst OJ, van Meijer M, Germeraad WT, Grimbergen J, van Den Doel MA, Vogels R, van Deutekom J, Janson AA, de Bruijn JD, Uytdehaag F, Quax PH, Logtenberg T, Mehtali M, Bout A

Abstract

Since targeting of recombinant adenovirus vectors to defined cell types in vivo is a major challenge in gene therapy and vaccinology, we explored the natural diversity in human adenovirus tissue tropism. Hereto, we constructed a library of Ad5 vectors carrying fibers from other human serotypes. From this library, we identified vectors that efficiently infect human cells that are important for diverse gene therapy approaches and for induction of immunity. For several medical applications (prenatal diagnosis, artificial bone, vaccination, and cardiovascular disease), we demonstrate the applicability of these novel vectors. In addition, screening cell types derived from different species revealed that cellular receptors for human subgroup B adenoviruses are not conserved between rodents and primates. These results provide a rationale for utilizing elements of human adenovirus serotypes to generate chimeric vectors that improve our knowledge concerning adenovirus biology and widen the therapeutic window for vaccination and many different gene transfer applications.

MeSH Terms
Adenoviruses, Human/classification,genetics Animals Bone and Bones Capsid/genetics Capsid Proteins Cardiovascular Diseases/prevention & control Cell Line Gene Transfer Techniques Genetic Therapy/methods Genetic Vectors Humans Mice Organ Culture Techniques Prenatal Diagnosis Rats Recombinant Fusion Proteins Serotyping Tissue Engineering Viral Vaccines
Chemicals
Capsid Proteins Recombinant Fusion Proteins Viral Vaccines hexon capsid protein, Adenovirus
Authors & Affiliations
16 authors, click to expand affiliations / ORCID
Havenga M J E
Crucell Holland B.V., 2301 CA Leiden, The Netherlands. [email protected]
Lemckert A A C
Ophorst O J A E
van Meijer M
Germeraad W T V
Grimbergen J
van Den Doel M A
Vogels R
van Deutekom J
Janson A A M
de Bruijn J D
Uytdehaag F
Quax P H A
Logtenberg T
Mehtali M
Bout A
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Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/jvi.76.9.4612-4620.2002
Email
[email protected]
Published
2002-05-00
Pages
4612-20
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC155076
Subset
IM
External Links
PubMed source DOI: 10.1128/jvi.76.9.4612-4620.2002 PMC Full Text View journal details
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