Nonviral jet-injection gene transfer for efficient in vivo cytosine deaminase suicide gene therapy of colon carcinoma

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Item Type:	Article
Title:	Nonviral jet-injection gene transfer for efficient in vivo cytosine deaminase suicide gene therapy of colon carcinoma
Creators Name:	Walther, W., Stein, U., Fichtner, I., Kobelt, D., Aumann, J., Arlt, F. and Schlag, P.M.
Abstract:	Jet-injection technology has developed into an efficient gene delivery system for nonviral in vivo gene transfer. In this study the jet-injector system was used for the intratumoral gene transfer of small volumes of naked DNA encoding the Escherichia coli cytosine deaminase (CD) suicide gene. In our in vivo studies human colon carcinoma (patient-derived tumor model Colo5734 and SW480 colon carcinoma)-bearing NMRI-nu/nu male mice received four jet injections (10 μl per injection) of the CD-gene-carrying plasmid, representing 40 μg plasmid DNA per animal. Forty-eight hours after jet-injection, treatment of tumors with 5-fluorocytosine (5-FC; 500 mg/kg ip) was started and during treatment tumor volumes were measured. Starting from day 5 of 5-FC treatment inhibition of tumor growth was seen in the CD-gene-transduced tumors compared to the respective control groups, which lasted for the entire observation time. Expression analysis at the mRNA and protein levels revealed efficient expression of the CD gene in the jet-injected tumors. Therefore, in this in vivo study jet-injection gene transfer of 40 μg CD-expressing naked plasmid DNA leads to a significant tumor growth inhibition. This study demonstrates the applicability of the jet-injection technology for in vivo gene transfer into tumors to achieve efficient tumor gene therapy.
Keywords:	Colon cancer, Cytosine Deaminase, Jet-Injection, Nonviral Gene Therapy, Suicide Gene, Animals, Mice
Source:	Molecular Therapy
ISSN:	1525-0016
Publisher:	Academic Press Inc Elsevier Science
Volume:	12
Number:	6
Page Range:	1176-1184
Date:	29 September 2005
Official Publication:	https://doi.org/10.1016/j.ymthe.2005.07.700
PubMed:	View item in PubMed

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