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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2001-12-25
pubmed:abstractText
Recombinant vectors based on adeno-associated virus (AAV) or human immunodeficiency 1 (lentivirus) are promising tools for long term in vivo gene delivery. Their design allows the exchange of capsids or envelopes, respectively, theoretically providing the opportunity to transduce a range of cell types. We constructed AAV vectors encoding enhanced green fluorescent protein (EGFP) within an AAV serotype 2 (AAV2) genome contained in an AAV2, five or one capsid (called AAV2/2, AAV2/5 and AAV2/1, respectively). Similarly we produced lentiviral vectors, encoding the same expression cassette present in the AAV vectors, pseudotyped with proteins from vesicular stomatitis virus glycoprotein (VSVG) or Mokola envelopes. Transduction characteristics of these vectors were evaluated in the murine retina following subretinal or intravitreal administration. The time of onset of transgene expression and the targeted cell types differed between the various recombinants. Onset of transgene expression was 3-4 days for lentiviral vectors and AAV2/1. In contrast, onset was at 2-4 weeks for AAV2/5 and AAV2/2, respectively. After subretinal injection, both lenti-VSVG and AAV2/5 transduced the retinal pigment epithelium (RPE) and photoreceptors efficiently whereas transgene expression was restricted to RPE cells using lenti with the Mokola envelope or AAV2/1. After intravitreal administration, only AAV2/2 and lenti-VSVG transduced the inner retina. Vector-mediated fluorescence was detected in the retina for over 12 weeks for all of the vectors. We conclude that pseudotyping provides a useful means to manipulate viral vector cell targeting specificity as well as retinal transduction characteristics of vectors containing the same genome.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0964-6906
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
3075-81
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:11751689-Animals, pubmed-meshheading:11751689-Antibody Formation, pubmed-meshheading:11751689-Capsid, pubmed-meshheading:11751689-Cytomegalovirus, pubmed-meshheading:11751689-Dependovirus, pubmed-meshheading:11751689-Gene Expression, pubmed-meshheading:11751689-Gene Therapy, pubmed-meshheading:11751689-Genetic Vectors, pubmed-meshheading:11751689-Green Fluorescent Proteins, pubmed-meshheading:11751689-Lentivirus, pubmed-meshheading:11751689-Luminescent Proteins, pubmed-meshheading:11751689-Membrane Glycoproteins, pubmed-meshheading:11751689-Membrane Proteins, pubmed-meshheading:11751689-Mice, pubmed-meshheading:11751689-Mice, Inbred C57BL, pubmed-meshheading:11751689-Photoreceptor Cells, pubmed-meshheading:11751689-Pigment Epithelium of Eye, pubmed-meshheading:11751689-Promoter Regions, Genetic, pubmed-meshheading:11751689-Retina, pubmed-meshheading:11751689-Transduction, Genetic, pubmed-meshheading:11751689-Viral Envelope Proteins
pubmed:year
2001
pubmed:articleTitle
Exchange of surface proteins impacts on viral vector cellular specificity and transduction characteristics: the retina as a model.
pubmed:affiliation
Institute for Human Gene Therapy, Department of Molecular and Cellular Engineering, The Wistar Institute, Philadelphia, PA, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't