Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
1998-10-23
pubmed:abstractText
We investigated whether directly injecting retroviral vectors into preimmune fetuses could result in the transfer and long-term expression of exogenous genes. Twenty-nine preimmune sheep fetuses were injected with helper-free retroviral vector preparations. Twenty-two fetuses survived to term, 4 of which were sacrificed at birth. Of the remaining 18 animals, 3 were controls and 15 had received vector preparations. Twelve of these 15 animals demonstrated transduction of hematopoietic cells when blood and marrow were analyzed by neo(r)-specific PCR. Eight experimental sheep have been followed for 5 years, during which time we have consistently observed proviral DNA and G418-resistant hematopoetic progenitors. The G418-resistant colonies were positive when analyzed by neo(r)-specific PCR. neo(r) gene expression was also demonstrated using several immunological and biochemical methods. The transduction of hematopoietic stem cells was confirmed when lambs transplanted with bone marrow from in utero-transduced sheep exhibited neo(r) activity in marrow and blood. Vector distribution was widespread in primary animals without pathology. PCR analysis indicates that the germ line was not altered. These studies demonstrate that direct injection of an engineered retrovirus is a feasible means of safely delivering a foreign gene to a developing fetus and achieving long-term expression without modifying the germ line of the recipient.
pubmed:grant
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
9
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1571-85
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed-meshheading:9694156-Animals, pubmed-meshheading:9694156-Blotting, Southern, pubmed-meshheading:9694156-Enzyme-Linked Immunosorbent Assay, pubmed-meshheading:9694156-Erythroid Precursor Cells, pubmed-meshheading:9694156-Female, pubmed-meshheading:9694156-Fetal Diseases, pubmed-meshheading:9694156-Fluorescent Antibody Technique, pubmed-meshheading:9694156-Gene Therapy, pubmed-meshheading:9694156-Gene Transfer Techniques, pubmed-meshheading:9694156-Genetic Vectors, pubmed-meshheading:9694156-Gentamicins, pubmed-meshheading:9694156-Hematopoietic Stem Cell Transplantation, pubmed-meshheading:9694156-In Situ Hybridization, Fluorescence, pubmed-meshheading:9694156-Injections, Intraperitoneal, pubmed-meshheading:9694156-Kanamycin Kinase, pubmed-meshheading:9694156-Polymerase Chain Reaction, pubmed-meshheading:9694156-Pregnancy, pubmed-meshheading:9694156-Retroviridae, pubmed-meshheading:9694156-Sequence Analysis, DNA, pubmed-meshheading:9694156-Sheep
pubmed:year
1998
pubmed:articleTitle
In utero gene therapy: transfer and long-term expression of the bacterial neo(r) gene in sheep after direct injection of retroviral vectors into preimmune fetuses.
pubmed:affiliation
Departments of Veterans Affairs Medical Center, Reno, NV 89520, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't