Suicide gene therapy using reducible poly (oligo-d-arginine) for the treatment of spinal cord tumors

Young Wook Won, Kyung Min Kim, Sung Su An, Minhyung Lee, Yoon Ha, Yong Hee Kim

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Suicide gene therapy based on a combination of herpes simplex virus-thymidine kinase (HSV-tk) and ganciclovir (GCV) has obstacles to achieving a success in clinical use for the treatment of cancer due to inadequate thymidine kinase (TK) expression. The primary concern for improving anticancer efficacy of the suicide gene therapy is to develop an appropriate carrier that highly expresses TK in vivo. Despite great advances in the development of non-viral vectors, none has been used in cancer suicide gene therapy, not even in experimental challenge. Reducible poly (oligo-d-arginine) (rPOA), one of the effective non-viral carriers working in vivo, was chosen to deliver HSV-tk to spinal cord tumors which are appropriate targets for suicide gene therapy. Since the system exerts toxicity only in dividing cells, cells in the central nervous system, which are non-proliferative, are not sensitive to the toxic metabolites. In the present study, we demonstrated that the locomotor function of the model rat was maintained through the tumor suppression resulting from the tumor-selective suicide activity by co-administration of rPOA/HSV-tk and GCV. Thus, rPOA plays a crucial role in suicide gene therapy for cancer, and an rPOA/HSV-tk and GCV system could help promote in vivo trials of suicide gene therapy.

Original languageEnglish
Pages (from-to)9766-9775
Number of pages10
JournalBiomaterials
Volume32
Issue number36
DOIs
Publication statusPublished - 2011 Dec 1

Fingerprint

Spinal Cord Neoplasms
Gene therapy
Arginine
Thymidine Kinase
Genetic Therapy
Suicide
Tumors
Viruses
Ganciclovir
Simplexvirus
Therapeutics
Neoplasms
Poisons
Neurology
Metabolites
Neoplasm Genes
Toxicity
Rats
Central Nervous System

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Ceramics and Composites
  • Biophysics
  • Biomaterials
  • Mechanics of Materials

Cite this

Won, Young Wook ; Kim, Kyung Min ; An, Sung Su ; Lee, Minhyung ; Ha, Yoon ; Kim, Yong Hee. / Suicide gene therapy using reducible poly (oligo-d-arginine) for the treatment of spinal cord tumors. In: Biomaterials. 2011 ; Vol. 32, No. 36. pp. 9766-9775.
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Suicide gene therapy using reducible poly (oligo-d-arginine) for the treatment of spinal cord tumors. / Won, Young Wook; Kim, Kyung Min; An, Sung Su; Lee, Minhyung; Ha, Yoon; Kim, Yong Hee.

In: Biomaterials, Vol. 32, No. 36, 01.12.2011, p. 9766-9775.

Research output: Contribution to journalArticle

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