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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1997-5-20
pubmed:abstractText
Recent reports have suggested that delivery of genes flanked by AAV ITRs may be useful for gene therapy of diseases that involve the brain. We have compared the efficiency of gene expression in vitro in CNS-derived cells from four different promoters when the transgene is flanked by AAV ITRs, using both transfection via cationic liposomes, and infection via rAAV. The human cytomegalovirus (CMV) immediate-early enhancer/promoter, the SV40 early enhancer/promoter, the JC polymovirus promoter, and the chicken beta-actin promoter coupled to the CMV enhancer were able to drive expression of the reporter gene beta-galactosidase in all tumor and primary brain cell cultures tested. Although the relative order of efficiency differed between cell types, the CMV promoter was always the strongest, generally by at least one order of magnitude. A comparison of the relative levels of expression seen between different cell types on transfection and infection suggest that not all CNS-derived cells are infected equally efficiently by rAAVs. High level of expression were seen within 24 h of transgene delivery by either transfection or infection, dropping dramatically within days. All cell types and promoters showed the same decline, suggesting that transient expression by rep-rAAVs may be efficient, but stable expression as detected in this system is a low frequency event. In vivo studies using the CMV promoter also suggest that although rep-rAAVs are able to infect efficiently CNS cells and produce high levels of gene expression shortly after transduction, the majority of such infections do not lead to stable high-level expression of transgenes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0969-7128
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
437-47
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Comparison of promoter strengths on gene delivery into mammalian brain cells using AAV vectors.
pubmed:affiliation
EK Shriver Center, Waltham, MA, USA.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, U.S. Gov't, P.H.S.