Linked Life Data

10446929

Source:http://linkedlifedata.com/resource/pubmed/id/10446929

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1999-10-28
pubmed:abstractText
The application of retroviruses generated from murine cells for in vivo gene therapy is restricted primarily because of the rapid inactivation of these viruses by the human complement system. To circumvent this disadvantageous property of murine retroviruses we have generated infectious amphotropic retroviruses that exhibit strong protection against human complement attack. The membrane of these viruses contains a fusion protein, DAFF2A, that is composed of the catalytic domain of the human complement regulatory protein (CRP) decay-accelerating factor (DAF) and the envelope protein of the amphotropic murine leukemia virus (MuLV) 4070A (EnvA). The fusion of two other CRPs, MCP and CD59, to the same amphotropic Env moiety did not lead to equivalent results. The fusion protein DAFF2A was stably expressed in mouse NIH 3T3-based helper cells and independently identified with either alpha-DAF MAb or alpha-Env PAb on the cell membrane. Western blot analysis confirmed the expected molecular weight of the fusion protein. Viral titers obtained from NIH 3T3 helper cell pools were 5 x 10(5) CFU for wild-type amphotropic EnvA virus and 1 x 10(5) CFU for DAFF2A virus, respectively. By blocking the catalytic domain of DAF by pretreatment with alpha-DAF MAb DAFF2A, recombinant virions could be converted to wild-type with respect to sensitivity against human serum. Since the method for producing virions that are protected against human serum should be applicable to any cell type it offers a novel tool for human in vivo gene therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
20
pubmed:volume
10
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1893-902
pubmed:dateRevised
2005-11-17
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
Complement-protected amphotropic retroviruses from murine packaging cells.
pubmed:affiliation
Department of Gene Regulation and Differentiation, GBF-National Research Center for Biotechnology, Braunschweig, Germany.
pubmed:publicationType
Journal Article