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Neural precursor cells for delivery of
replication-conditional HSV-1 vectors to intracerebral gliomas
Herrlinger U, Woiciechowski C, Sena-Esteves M, Aboody KS, Jacobs AH, Rainov
NG, Snyder EY, Breakefield XO
Neurology Service, Massachusetts General Hospital and Harvard
Medical School, Charlestown 02129, USA.
Cellular delivery of a replication-conditional herpes simplex virus type 1
(HSV-1) vector provides a means for gene therapy of invasive tumor cells.
LacZ-bearing neural precursor cells, which can migrate and differentiate in the
brain, were infected with a ribonucleotide reductase-deficient HSV-1 mutant
virus (rRp450) that replicates only in dividing cells.
Replication of rRp450 in neural precursor cells was blocked prior to
implantation into the tumor by growth arrest in late G1 phase through treatment
with mimosine.
Viral titers in the medium of mimosine-treated, rRp450-infected neural precursor
cells were below detection levels 3 days after infection.
In culture, after removal of mimosine and passaging, cells resumed growth and
replication of rRp450 so that, 7 days later, virus was present in the medium and
cell death was evident.
Mimosine-treated neural precursor cells injected into established intracerebral
CNS-1 gliomas in nude mice migrated extensively throughout the tumor and into
the surrounding parenchyma beyond the tumor over 3 days.
Mimosine-treated neural precursor cells, infected with rRp450 and injected into
intracerebral CNS-1 tumors, also migrated within the tumor with the appearance
of foci of HSV-thymidine kinase-positive (TK+) cells, presumably including tumor
cells, distributed throughout the tumor and in the surrounding parenchyma over a
similar period.
This migratory cell delivery method has the potential to expand the range of
delivery of HSV-1 vectors to tumor cells in the brain.
PMID: 10933953 [PubMed - indexed for MEDLINE]
Source: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=10933953
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