ArticleMolecular therapy : the journal of the American Society of Gene Therapy2003
Optimization of adenoviral vectors to direct highly amplified prostate-specific expression for imaging and gene therapy.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 52 citations in OpenAlex.
- A molecular imaging system based on both transcriptional and genomic amplification to detect prostate cancer cells in vivo.Molecular therapy : the journal of the American Society of Gene Therapy · 2013Article
- Molecular imaging of prostate cancer: PET radiotracers.AJR. American journal of roentgenology · 2012Review
- Optical imaging for stem cell differentiation to neuronal lineage.Nuclear medicine and molecular imaging · 2012Review
- Androgen-independent molecular imaging vectors to detect castration-resistant and metastatic prostate cancer.Cancer research · 2011Article
- Lentiviral vectors with amplified beta cell-specific gene expression.Gene therapy · 2009Article
- A potent, imaging adenoviral vector driven by the cancer-selective mucin-1 promoter that targets breast cancer metastasis.Clinical cancer research : an official journal of the American Association for Cancer Research · 2009Article
- Noninvasive imaging of therapeutic gene expression using a bidirectional transcriptional amplification strategy.Molecular therapy : the journal of the American Society of Gene Therapy · 2008Article
- Configurations of a two-tiered amplified gene expression system in adenoviral vectors designed to improve the specificity of in vivo prostate cancer imaging.Gene therapy · 2008Article
- Advances in preclinical investigation of prostate cancer gene therapy.Molecular therapy : the journal of the American Society of Gene Therapy · 2007Review
- Isolation of a novel mouse gene, mSVS-1/SUSD2, reversing tumorigenic phenotypes of cancer cells in vitro.Cancer science · 2007Article
- Two-step amplification of the human PPT sequence provides specific gene expression in an immunocompetent murine prostate cancer model.Cancer gene therapy · 2007Article
- Gene expression and gene therapy imaging.European radiology · 2007Review
- Two-step transcriptional amplification-lipid-based nanoparticles using PSMA or midkine promoter for suicide gene therapy in prostate cancer.Cancer science · 2006Article
- Specific targeting of gene therapy to prostate cancer using a two-step transcriptional amplification system.Future oncology (London, England) · 2006Review
- Functionality of androgen receptor-based gene expression imaging in hormone refractory prostate cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2005Article
- Gene therapy progress and prospects: noninvasive imaging of gene therapy in living subjects.Gene therapy · 2004Review
- Article
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Gene expression-based imaging coupled to gene therapy will permit the prediction of therapeutic outcome. A significant challenge for successful gene therapy is to achieve a high-level of specific gene expression; however, tissue-specific promoters are weak. We postulate that if the weak activity of tissue-specific promoters can be amplified to the levels of strong viral promoters, which have been successful in preclinical scenarios, while retaining specificity, the therapeutic index of gene therapy can be greatly augmented. With this in mind, we developed a two-step transcriptional activation (TSTA) system. In this two-tiered system, a modified prostate-specific antigen promoter was employed to drive a potent synthetic transcriptional activator, GAL4-VP2. This, in turn, activated the expression of a GAL4-dependent reporter or therapeutic gene. Here we demonstrate that recombinant adenoviral vectors (Ads) in which we have incorporated prostate-targeted TSTA expression cassettes retain cell specificity and androgen responsiveness in cell culture and in animal models, as measured by noninvasive optical bioluminescence imaging. We investigated the mechanism of TSTA in different adenoviral configurations. In one configuration, both the activator and the reporter components are inserted into a single Ad (AdTSTA-FL). The activity of AdTSTA-FL exceeds that of a cytomegalovirus promoter-driven vector (AdCMV-FL), while maintaining tissue specificity. When the activator and reporter components are placed in two separate Ads, androgen induction is more robust than for the single AdTSTA-FL. Based on these findings, we hope to refine the TSTA Ads further to improve the efficacy and safety of prostate cancer gene therapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.