Gene silencing by adenovirus‐delivered siRNA

Shen, Changxian; Buck, Andreas K.; Liu, Xiangwei; Winkler, Michael; Reske, Sven N.

doi:10.1016/s0014-5793(03)00209-6

Cited by 179 publications

(107 citation statements)

References 20 publications

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“…36,37 To facilitate the application of siRNA in cancer gene therapy, it is necessary to develop improved approaches for efficient introduction of siRNA into target cells. 38,39 Viral vectors are efficient transgene-carrying systems, and previous studies have shown the antitumor ability of viral vectors in vitro and in vivo by using replication-deficient adenovirus. 39,41 Recombinant adenovirus is valuable particularly for transgene expression in hard-to-transfect cells and has been used widely in clinical and experimental conditions.…”

Section: Discussionmentioning

confidence: 99%

Survivin knockdown by short hairpin RNA abrogates the growth of human hepatocellular carcinoma xenografts in nude mice

Zhang

Zheng

et al. 2009

Cancer Gene Ther

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Abnormal high activation of survivin is involved in carcinogenesis of various types of cancer. Survivin has been shown to promote cell proliferation in human hepatocellular carcinoma (HCC). Survivin-targeting approaches have become a promising strategy for treating HCC. Here, we used a reporter system to screen effective survivin siRNA sequences. The effect of vector-based survivin short hairpin RNA (shRNA) on the malignant phenotype of HCC cells in vitro and in vivo was determined, and an adenovirusmediated shRNA expression vector was developed to decrease survivin expression of the established HCC tumor in nude mice. In vitro study showed that stable survivin knockdown inhibited cancer cell proliferation, enhanced apoptotic susceptibility, arrested cell cycle in the G1 phase and resulted in apparent mitotic catastrophe. Moreover, cells stably expressing survivin shRNA showed decreased tumorigenicity in nude mice. An additional in vivo study showed that intratumoral injection of adenovirus-delivered survivin shRNA suppressed tumor growth by spontaneous apoptosis of cancer cells and significantly prolonged animal survival. In conclusion, we proved the therapeutic potential of survivin shRNA for the treatment of HCC. And our results indicated that adenovirus-delivered shRNA may serve as a novel therapeutic for HCC.

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Section: Discussionmentioning

confidence: 99%

Survivin knockdown by short hairpin RNA abrogates the growth of human hepatocellular carcinoma xenografts in nude mice

Zhang

Zheng

et al. 2009

Cancer Gene Ther

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“…Adenoviral vectors are widely used both in cells and in vivo; however, their inability to integrate into the genome has proved advantageous in terms of safety but at the cost of inefficient long-term gene silencing. [83][84][85][86][87][88][89] However, other disadvantages of using adenovirus for gene therapy are well known, including high immunogenicity and proinflammatory effects. In contrast, the adenovirus-associated viruses have been more effective in 92 Hydrodynamic injections of siRNAs alone or in conjunction with reporter constructs have led to the silencing of endogenous genes in various animal tissues, which include liver, spleen, lung, kidney and pancreas.…”

Section: Rnai Deliverymentioning

confidence: 99%

siRNA-based approaches in cancer therapy

2006

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The availability of the human genome sequence has revolutionized the strategy of employing nucleic acids with sequences complementary to specific target genes to improve drug discovery and target validation. Development of sequence-specific DNA or RNA analogs that can block the activity of selected single-stranded genetic sequences offers the possibility of rational design with high specificity, lacking in many current drug treatments for various diseases including cancer, at relatively inexpensive costs. Antisense technology is one such example that has shown promising results and boasts of yielding the only approved drug to date in the genomics field. However, in vivo delivery issues have yet to be completely overcome for widespread clinical applications. In contrast to antisense oligonucleotides, the mechanism of silencing an endogenous gene by the introduction of a homologous double-stranded RNA (dsRNA), transgene or virus is called post-transcriptional gene silencing (PTGS) or RNA interference. PTGS is a natural mechanism whereby metazoan cells suppress expansion of genes when they come across dsRNA molecules with the same sequence. Short interfering RNA is currently the fastest growing sector of this antigene field for target validation and therapeutic applications. Although, in theory, the development of genomics-based agents to inhibit gene expression is simple and straightforward, the fundamental concern relies upon the capacity of the oligonucleotide to gain access to the target RNA. This paper summarizes the advances in the last decade in the field of PTGS using RNA interference approaches and provides relevant comparisons with other oligonucleotide-based approaches with a specific focus on oncology applications. Cancer Gene Therapy (2006) Genomic-based strategiesThe American Cancer Society estimates that, in 2005, a total of 1 372 910 new cancer cases and 570 280 deaths are expected in the United States. 1 These morbid statistics demonstrate the necessity of newer therapeutic modalities for achieving successful cancer treatment and cure. Downregulation of genes that contribute to cancer progression has been the goal of targeted genomics-based strategies, with the expectation that such an approach may lead to selective and specific inhibition of tumor growth with minimal untoward side effects on normal cells. Identification of target genes involved in neoplastic transformation and tumor progression has triggered the idea that nucleotide sequences of cancer-relevant genes could lead to the development of tailored anticancer agents that lack many of the toxic side effects of traditional cytotoxic drugs. This has led to a recent acceleration in the development and optimization of genomic-based strategies for cancer therapy. This idea dates back to the 1960s when RNA sequences were shown to serve as endogenous inhibitors of gene expression in procaryotes. The antigene approaches include the following:(1) Ribozymes: 2,3 These were discovered in the 1970s, and the elucidation of the transactivating hammerh...

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“…Then, we employed the newly developed adenovirus-delivered small interfering RNA (siRNA) technique (24) to study the effects of knockdown of c-Met on hepatocellular carcinoma cell growth in vitro and in vivo.…”

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confidence: 99%

Knockdown of c-Met by adenovirus-delivered small interfering RNA inhibits hepatocellular carcinoma growth in vitro and in vivo

Zhang

Pan

et al. 2005

Molecular Cancer Therapeutics

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c-Met is highly expressed and constitutively activated in various human tumors. We employed adenovirus-mediated RNA interference technique to knock down c-Met expression in hepatocellular carcinoma cells and observed its effects on hepatocellular carcinoma cell growth in vitro and in vivo. Among the five hepatocellular carcinoma and one normal human liver cell lines we analyzed, c-Met was highly expressed and constitutively tyrosine phosphorylated in only MHCC97-L and HCCLM3 hepatocellular carcinoma cells. Knockdown of c-Met could inhibit MHCC97-L cells proliferation by arresting cells at G 0 -G 1 phase. Soft agar colony formation assay indicated that the colony forming ability of MHCC97-L cells decreased by f70% after adenovirus AdH1-small interfering RNA (siRNA)/met infection. In vivo experiments showed that adenovirus AdH1-siRNA/met inhibited the tumorigenicity of MHCC97-L cells and significantly suppressed tumor growth when injected directly into tumors. These results suggest that knockdown of c-Met by adenovirus-delivered siRNA may be a potential therapeutic strategy for treatment of hepatocellular carcinoma in which c-Met is overexpressed. [Mol Cancer Ther 2005;4(10):1577 -84]

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Gene silencing by adenovirus‐delivered siRNA

Cited by 179 publications

References 20 publications

Survivin knockdown by short hairpin RNA abrogates the growth of human hepatocellular carcinoma xenografts in nude mice

Survivin knockdown by short hairpin RNA abrogates the growth of human hepatocellular carcinoma xenografts in nude mice

siRNA-based approaches in cancer therapy

Knockdown of c-Met by adenovirus-delivered small interfering RNA inhibits hepatocellular carcinoma growth in vitro and in vivo

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