Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-2-22
pubmed:abstractText
Peripheral nervous system (PNS) sensory neurons are directly involved in the pathophysiology of numerous inherited and acquired neurological conditions. Therefore, efficient and stable gene delivery to these postmitotic cells has significant therapeutic potential. Among contemporary vector systems capable of neuronal transduction, only those based on herpes simplex virus have been extensively evaluated in PNS neurons. We therefore investigated the transduction performance of recombinant adeno-associated virus type 2 (AAV) and VSV-G-pseudotyped lentivirus vectors derived from human immunodeficiency virus (HIV-1) in newborn mouse and fetal human dorsal root ganglia (DRG) sensory neurons. In dissociated mouse DRG cultures both vectors achieved efficient transduction of sensory neurons at low multiplicities of infection (MOIs) and sustained transgene expression within a 28-day culture period. Interestingly, the lentivirus vector selectively transduced neurons in murine cultures, in contrast to human cultures, in which Schwann and fibroblast-like cells were also transduced. Recombinant AAV transduced all three cell types in both mouse and human cultures. After direct microinjection of murine DRG explants, maximal transduction efficiencies of 20 and 200 transducing units per neuronal transductant were achieved with AAV and lentivirus vectors, respectively. Most importantly, both vectors achieved efficient and sustained transduction of human sensory neurons in dissociated cultures, thereby directly demonstrating the exciting potential of these vectors for gene therapy applications in the PNS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1043-0342
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
77-86
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11177545-Animals, pubmed-meshheading:11177545-Cells, Cultured, pubmed-meshheading:11177545-Dependovirus, pubmed-meshheading:11177545-Ganglia, Spinal, pubmed-meshheading:11177545-Gene Expression, pubmed-meshheading:11177545-Gene Targeting, pubmed-meshheading:11177545-Gene Transfer Techniques, pubmed-meshheading:11177545-Genetic Vectors, pubmed-meshheading:11177545-Green Fluorescent Proteins, pubmed-meshheading:11177545-Humans, pubmed-meshheading:11177545-Immunoenzyme Techniques, pubmed-meshheading:11177545-Infant, Newborn, pubmed-meshheading:11177545-Lentivirus, pubmed-meshheading:11177545-Luminescent Proteins, pubmed-meshheading:11177545-Membrane Glycoproteins, pubmed-meshheading:11177545-Mice, pubmed-meshheading:11177545-Microscopy, Fluorescence, pubmed-meshheading:11177545-Neurons, Afferent, pubmed-meshheading:11177545-Recombinant Proteins, pubmed-meshheading:11177545-Transduction, Genetic, pubmed-meshheading:11177545-Viral Envelope Proteins
pubmed:year
2001
pubmed:articleTitle
Adeno-associated virus and lentivirus vectors mediate efficient and sustained transduction of cultured mouse and human dorsal root ganglia sensory neurons.
pubmed:affiliation
Gene Therapy Research Unit of the Children's Hospital at Westmead and Children's Medical Research Institute, Westmead, NSW, Australia, 2145.
pubmed:publicationType
Journal Article, Comparative Study, Research Support, Non-U.S. Gov't