Neoplastic reversion accomplished by high efficiency adenoviral-mediated delivery of an anti-ras ribozyme.
Strategies have been developed to abrogate the aberrant expression of dominant oncogenes as a means to accomplish targeted tumor eradication. We have demonstrated previously the utility of this approach using a hammerhead ribozyme designed to cleave the mutant sequence in codon 12 of the activated H-ras oncogene transcript. To develop this strategy into a practical means to approach malignant disease, methods must be developed to accomplish high efficiency delivery of the ribozyme to target neoplastic cells. To accomplish this, a recombinant adenovirus was designed that encoded a gene cassette for the H-ras ribozyme. By using this virus, it was possible to accomplish high efficiency reversion of the neoplastic phenotype in mutant H-ras expressing tumor cells without the need for any selection steps. The demonstration of the utility of adenoviral-mediated delivery of anticancer ribozymes will allow the practical development of gene therapy strategies on this basis.
Feng
M
M
Gene Therapy Program, University of Alabama at Birmingham 35294, USA.
Cabrera
G
G
Deshane
J
J
Scanlon
K J
KJ
Curiel
D T
DT
D000256:Adenoviridae / Q000201:enzymology / Q000235:genetics; D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000235:genetics; D003062:Codon / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000235:genetics*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008969:Molecular Sequence Data; D016337:RNA, Catalytic / Q000008:administration & dosage* / Q000235:genetics; D014162:Transfection / Q000235:genetics / Q000379:methods; D014407:Tumor Cells, Cultured; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000628:therapy
D003062:Codon; D016337:RNA, Catalytic