In vivo characterization of horseradish peroxidase with indole-3-acetic acid and 5-bromoindole-3-acetic acid for gene therapy of cancer

Tupper, Joanna; Stratford, Michael R.L.; Hill, Sally A.; Tozer, Gillian M.; Dachs, Gabi U.

doi:10.1038/cgt.2009.86

Cited by 31 publications

(28 citation statements)

References 27 publications

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“…Mice in the Ad‐C6‐hTERT‐HRP plus IR group also had longer survival compared with controls. A recent study characterized the HRP/IAA system in vivo for gene therapy and indicated that HRP‐expressing tumors had a modest growth delay when treated with IAA compared with drug vehicle controls, but the treatment response could not be improved by combining HRP‐directed gene therapy with fractionated radiotherapy 29. However, in the current study, we demonstrated that the combination of gene therapy mediated by chimeric promoters with radiotherapy increased the antitumor effect.…”

Section: Discussioncontrasting

confidence: 55%

Novel, chimeric, cancer‐specific, and radiation‐inducible gene promoters for suicide gene therapy of cancer

Xiong

Sun

Wang

et al. 2011

Cancer

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BACKGROUND: Although the promoter of the human telomerase reverse transcriptase (hTERT) gene has been widely used in gene therapy for targeted cancer cells, it has some limitations for clinical use because of its low activity and potential toxicity to certain normal cells. To overcome these defects, the authors generated novel chimeric hTERT promoters that contained the radiation‐inducible sequence CC(A/T)6GG (known as CArG elements). METHODS: Chimeric hTERT promoters were synthesized that contained different numbers of CArG elements, and the activity of chimeric promoters was assessed in different cancer cell lines and normal cells. The potential of selected promoters to successfully control horseradish peroxidase (HRP) and prodrug indole‐3‐acetic acid (IAA) suicide gene therapy was tested in vitro and in vivo. RESULTS: The promoter activity assays indicated that the synthetic promoter that contained 6 repeating CArG units had the best radiation inducibility than any other promoters that contained different numbers of CArG units, and the chimeric promoters retained their cancer‐specific characteristics. The chimeric promoter was better at driving radiation‐inducible gene therapy than the control promoters. The sensitizer enhancement ratio of the chimeric promoter system determined by clonogenic assay was higher, and the chimeric promoter system resulted in a significantly higher apoptotic level compared with other promoter systems. The combination of chimeric/promoter‐mediated gene therapy and radiotherapy significantly inhibited tumor volume in a xenograft mouse model and resulted in a significant prolongation of survival in mice. CONCLUSIONS: The current results indicated that a combinational cancer‐specific promoter system that is responsive to irradiation has great potential for improving the efficacy of cancer treatment. Cancer 2011;. © 2011 American Cancer Society.

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Section: Discussioncontrasting

confidence: 55%

Novel, chimeric, cancer‐specific, and radiation‐inducible gene promoters for suicide gene therapy of cancer

Xiong

Sun

Wang

et al. 2011

Cancer

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“…The total combined daily dose of IAA for a 20 g mouse drinking 3 ml of IAA water (75 mg/kg) and receiving a 0.2 ml IAA gavage (125 mg/kg) was 200 mg/kg. This dose was selected since mice can tolerate up to 200 mg/kg/day IAA without obviously affecting health or body weight (Tupper et al, 2010). The number of mice per group (n) and experimental trials (N) was based on a historical precedent for establishing survival curves for virulent strains of T. gondii in mice (Su et al, 2002).…”

Section: Star Methodsmentioning

confidence: 99%

Essential cGMP Signaling in Toxoplasma Is Initiated by a Hybrid P-Type ATPase-Guanylate Cyclase

Brown

Sibley

2018

Cell Host & Microbe

108

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Summary (150) Apicomplexan parasites rely on cyclic nucleotide-dependent kinases for host cell infection, yet the mechanisms that control their activation remain unknown. Here we show that an apically-localized guanylate cyclase (GC) controls microneme secretion and lytic growth in the model apicomplexan Toxoplasma gondii. Cell permeable cGMP reversed the block in microneme secretion seen in a knockdown of TgGC, linking its function to production of cGMP. TgGC possesses an N-terminal P-type-ATPase domain fused to a C-terminal heterodimeric guanylate cyclase domain, an architecture found only in Apicomplexa and related protists. Complementation with a panel of mutants revealed a critical requirement for the P-type ATPase domain for maximum GC function. We further demonstrate that knockdown of TgGC in vivo protects mice from lethal infection by blocking parasite expansion and dissemination. Collectively this work demonstrates that cGMP-mediated signaling in Toxoplasma relies on a multi-domain architecture, which may serve a conserved role in related parasites.

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“…As a model we loaded horseradish peroxidase (HRP) into the cavities of PMOXA 6 ‐PDMS 44 ‐PMOXA 6 polymersomes that contained the bacterial outer membrane protein F (OmpF) in the membrane to control passage of specific substrates and products. We selected HRP because of its biological role in detoxification of H 2 O 2 , known as toxic by‐products of mitochondrial respiration in eukaryotic cells, and its role in modulating the protein function of by thiol oxidation . More recently, HRP has also gained significant interest in cancer research.…”

Section: Mf With Architecture and Functionality As Cell Mimicsmentioning

confidence: 99%

Bioinspired Molecular Factories with Architecture and In Vivo Functionalities as Cell Mimics

et al. 2020

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Despite huge need in the medical domain and significant development efforts, artificial cells to date have limited composition and functionality. Although some artificial cells have proven successful for producing therapeutics or performing in vitro specific reactions, they have not been investigated in vivo to determine whether they preserve their architecture and functionality while avoiding toxicity. Here, these limitations are overcome and customizable cell mimic is achieved—molecular factories (MFs)—by supplementing giant plasma membrane vesicles derived from donor cells with nanometer‐sized artificial organelles (AOs). MFs inherit the donor cell's natural cytoplasm and membrane, while the AOs house reactive components and provide cell‐like architecture and functionality. It is demonstrated that reactions inside AOs take place in a close‐to‐nature environment due to the unprecedented level of complexity in the composition of the MFs. It is further demonstrated that in a zebrafish vertebrate animal model, these cell mimics show no apparent toxicity and retain their integrity and function. The unique advantages of highly varied composition, multicompartmentalized architecture, and preserved functionality in vivo open new biological avenues ranging from the study of biorelevant processes in robust cell‐like environments to the production of specific bioactive compounds.

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In vivo characterization of horseradish peroxidase with indole-3-acetic acid and 5-bromoindole-3-acetic acid for gene therapy of cancer

Cited by 31 publications

References 27 publications

Novel, chimeric, cancer‐specific, and radiation‐inducible gene promoters for suicide gene therapy of cancer

Novel, chimeric, cancer‐specific, and radiation‐inducible gene promoters for suicide gene therapy of cancer

Essential cGMP Signaling in Toxoplasma Is Initiated by a Hybrid P-Type ATPase-Guanylate Cyclase

Bioinspired Molecular Factories with Architecture and In Vivo Functionalities as Cell Mimics

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