γ-Rays enhance rAAV-mediated transgene expression and cytocidal effect of AAV-HSVtk/ganciclovir on cancer cells View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

2001-02-01

AUTHORS

Takeharu Kanazawa, Masashi Urabe, Hiroaki Mizukami, Takashi Okada, Akihiro Kume, Hiroshi Nishino, John Monahan, Ken Kitamura, Keiichi Ichimura, Keiya Ozawa

ABSTRACT

Adeno-associated virus (AAV) vector has several unique properties suited for gene therapy applications. However, relatively low efficiency of transgene expression, which is mainly due to a limited second-strand synthesis from the single-stranded AAV genome, can be a problem in some applications that require potent gene expression such as antitumor applications. Recently, γ-ray irradiation has been reported to enhance the second-strand synthesis of the AAV genome, and consequently transgene expression. We demonstrate here that an AAV vector harboring the herpes simplex virus type-1 thymidine kinase (HSVtk) is able to kill cancer cells more efficiently when used in combination with γ-ray irradiation. A human maxillary sinus cancer cell line, NKO-1, was efficiently killed in combination with HSVtk transduction and ganciclovir (GCV), as expected. More importantly, γ-ray irradiation of practical dosages augmented the cytocidal effect of the HSVtk/GCV system. Southern analysis indicated that γ-rays enhanced the double-strand synthesis of the rAAV genome in NKO-1 cells. These findings suggest that the combination of rAAVtk/GCV suicide gene therapy with radiotherapy has synergistic effects in the treatment of cancers and may lead to a reduction of the potential toxicity of both rAAVtk/GCV and γ-ray irradiation. Cancer Gene Therapy (2001) 8, 99–106 More... »

PAGES

99-106

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.cgt.7700282

DOI

http://dx.doi.org/10.1038/sj.cgt.7700282

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1017788637

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11263531


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