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Adenovirus-mediated transfer of siRNA against survivin induced apoptosis and attenuated tumor cell growth in vitro and in vivo.
- Source :
-
Molecular therapy : the journal of the American Society of Gene Therapy [Mol Ther] 2004 Jul; Vol. 10 (1), pp. 162-71. - Publication Year :
- 2004
-
Abstract
- Gene targeting using short interfering RNA (siRNA) has become a common strategy to explore gene function because of its prominent efficacy and specificity. For the application of siRNA technology to gene therapy, however, still more efficient transduction of siRNA into target cells is needed. In this study, we developed an adenoviral vector harboring a tandem-type siRNA expression unit, in which sense and antisense strands composing the siRNA duplex were separately transcribed by two human U6 promoters. Targeting survivin, an antiapoptotic molecule widely overexpressed in malignancies but not detected in terminally differentiated adult tissues, this type of adenoviral vector (Adv-siSurv) successfully exerted a gene knockdown effect and induced apoptosis in HeLa, U251, and MCF-7 cells. These cancer cells, once infected with Adv-siSurv, displayed remarkably attenuated growth potential, both in vitro and in vivo. Moreover, intratumoral injection of Adv-siSurv significantly suppressed tumor growth in a xenograft model using U251 glioma cells. This novel modality may be a promising tool for cancer therapy.
- Subjects :
- Animals
Cell Line, Tumor
Cell Proliferation
Gene Targeting
Genetic Therapy methods
Genetic Vectors genetics
Humans
Inhibitor of Apoptosis Proteins
Mice
Mice, Inbred Strains
Microtubule-Associated Proteins genetics
Microtubule-Associated Proteins metabolism
Neoplasm Proteins
Neoplasms pathology
RNA, Small Interfering metabolism
Survivin
Xenograft Model Antitumor Assays
Adenoviridae genetics
Apoptosis
Microtubule-Associated Proteins antagonists & inhibitors
Neoplasms therapy
RNA, Small Interfering genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1525-0016
- Volume :
- 10
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- Molecular therapy : the journal of the American Society of Gene Therapy
- Publication Type :
- Academic Journal
- Accession number :
- 15233951
- Full Text :
- https://doi.org/10.1016/j.ymthe.2004.05.006