Use of H19 regulatory sequences for targeted gene therapy in cancer

Int J Cancer. 2002 Apr 10;98(5):645-50. doi: 10.1002/ijc.10243.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Diphtheria Toxin / adverse effects
  • Diphtheria Toxin / genetics*
  • Diphtheria Toxin / therapeutic use
  • Female
  • Ganciclovir / pharmacology
  • Gene Transfer Techniques
  • Genetic Therapy / methods*
  • Genetic Vectors
  • Herpesvirus 1, Human / enzymology*
  • Herpesvirus 1, Human / genetics
  • Humans
  • Luciferases / metabolism
  • Mice
  • Mice, Inbred C3H
  • Neoplasm Transplantation
  • Neoplasms / therapy*
  • Peptide Fragments / adverse effects
  • Peptide Fragments / genetics*
  • Peptide Fragments / therapeutic use
  • Promoter Regions, Genetic / genetics
  • RNA, Long Noncoding
  • RNA, Untranslated / genetics*
  • RNA, Untranslated / metabolism
  • Regulatory Sequences, Nucleic Acid / genetics*
  • Thymidine Kinase / adverse effects
  • Thymidine Kinase / genetics*
  • Thymidine Kinase / therapeutic use
  • Tumor Cells, Cultured
  • Urinary Bladder Neoplasms / genetics
  • Urinary Bladder Neoplasms / therapy*


  • Diphtheria Toxin
  • H19 long non-coding RNA
  • Peptide Fragments
  • RNA, Long Noncoding
  • RNA, Untranslated
  • diphtheria toxin fragment A
  • Luciferases
  • Thymidine Kinase
  • Ganciclovir