miR-122a-Regulated Expression of a Suicide Gene Prevents Hepatotoxicity Without Altering Antitumor Effects in Suicide Gene Therapy

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Regulation of HSVtk gene by endogenous microRNA-122a in liver cell lines as suicide gene therapy

Aim Here, we use miR-122a that exhibits liver-specific expression for developing a post-transcriptional regulative system mediated by microRNAs. Background Gene therapy with adenovirus (Ad) vectors that express herpes simplex virus thymidine kinase (HSVtk) and ganciclovir (GCV) have been suggested as a therapeutic strategy to cancer. However, Ad vectors injected into tumors are dispersed into...

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Evaluation of miR-122-regulated suicide gene therapy for hepatocellular carcinoma in an orthotopic mouse model.

OBJECTIVE Intratumoral administration of adenoviral vector encoding herpes simplex virus (HSV) thymidine kinase (TK) gene (Ad-TK) followed by systemic ganciclovir (GCV) is an effective approach in treating experimental hepatocellular carcinoma (HCC). However, hepatotoxicity due to unwanted vector spread and suicide gene expression limited the application of this therapy. miR-122 is an abundant,...

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Suicide Gene Therapy against Cancer

A major limitation of conventional chemotherapies used in cancer treatments today are low therapeutic indices and side effects that result from drug effects on normal tissues (off target). One of the most innovative approaches to developing antineoplastic agents with increased tumor selectivity is the use of suicide gene therapy. Suicide gene therapy involves delivering a gene product in proxim...

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Use of suicide genes in gene therapy.

Gene therapy encompasses a broad range of treatment modalities that may eventually be applied to a variety of genetic as well as acquired diseases. In addition to compensating for a defective gene--and enhancing a cellular function--gene transfer can allow for a conditional negative selection of target cells. Indeed, the transfer of a gene encoding a susceptibility factor can make a cell specif...

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ژورنال

عنوان ژورنال: Molecular Therapy

سال: 2008

ISSN: 1525-0016

DOI: 10.1038/mt.2008.159