Linked Life Data

17176210

Source:http://linkedlifedata.com/resource/pubmed/id/17176210

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-2-2
pubmed:abstractText
Recombinant adeno-associated virus (rAAV)-mediated gene transfer has shown promise for treating diseases in various animal models including the mdx mouse model of Duchenne muscular dystrophy (DMD). In many cases, however, preclinical studies in inbred mice have not successfully predicted human clinical responses. To assess the potential clinical utility of treating human DMD patients by AAV-mediated gene delivery, we performed a series of direct intramuscular injections in random-bred wild-type dogs. AAV serotypes 2 and 6 carrying different promoter-transgene cassettes were produced as previously described for murine studies and administered intramuscularly. The injection sites were biopsied at various time points and analyzed for transgene expression and immunohistochemical analysis. In contrast to the generally nonimmunogenic nature of these vectors in murine studies, both AAV2 and AAV6 vectors elicited robust cellular immune responses regardless of the transgene expressed, the cellular specificity of the promoter, and the muscle type injected. Viral purification by various methods did not diminish T cell-mediated infiltration. Our data indicate that AAV2 and AAV6 capsid proteins can elicit primary cellular immune responses when injected into the skeletal muscle of random-bred dogs, and suggest the possibility of cellular immunity to AAV vectors in humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18-26
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Immunity to adeno-associated virus-mediated gene transfer in a random-bred canine model of Duchenne muscular dystrophy.
pubmed:affiliation
Program in Transplantation Biology, Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural