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Use of H19 regulatory sequences for targeted gene therapy in cancer
Author(s) -
Ohana Patricia,
Bibi Osaat,
Matouk Imad,
Levy Carol,
Birman Tatiana,
Ariel Ilana,
Schneider Tamar,
Ayesh Suhail,
Giladi Hilla,
Laster Morris,
de Groot Nathan,
Hochberg Abraham
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10243
Subject(s) - genetic enhancement , transfection , gene , biology , cancer research , diphtheria toxin , vector (molecular biology) , regulator gene , regulatory sequence , thymidine kinase , cancer , gene expression , bladder cancer , herpes simplex virus , cell culture , virus , immunology , genetics , toxin , recombinant dna
We present a tumor gene therapy approach based on the use of regulatory sequences of the H19 gene that are differentially expressed between normal and cancer cells. We constructed expression vectors carrying the gene for the A fragment of diphtheria toxin (DT‐A) or herpes simplex virus thymidine kinase (HSV‐ tk ), under the control of a 814 bp 5′‐flanking region of the H19 gene. The cell killing activity of these constructs was in accordance with the relative activity of the H19 regulatory sequences in the transfected cells. We evaluated the therapeutic potential of the gene expression constructs driven by H19 regulatory sequences in an animal model of bladder cancer induced by subcutaneous injection of syngeneic bladder tumor cell lines. Intratumoral injection of these constructs caused a significant suppression of subcutaneous tumor growth, with no obvious toxicity toward the host. © 2002 Wiley‐Liss, Inc.