Publications (27) View all
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Article: History of gene therapy.
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ABSTRACT: Two decades after the initial gene therapy trials and more than 1700 approved clinical trials worldwide we not only have gained much new information and knowledge regarding gene therapy in general, but also learned to understand the fear that has persisted in the society. Despite the drawbacks gene therapy has faced, also success stories have been reported. Examples for these are the positive recommendation for a gene therapy product (Glybera) by the EMA for approval in the European Union and the positive trials for the treatment of ADA deficiency, SCID-X1 and adrenoleukodystrophy. Nevertheless, there is still a lot to learn and during the course of time more safety data has become available that helps us to develop better gene therapy approaches. Also, with the increased understanding of molecular medicine, we have been able to develop more specific and efficient gene transfer vectors. In this review, we will take a historical view and highlight some of the milestones that had an important impact on the development of gene therapy. We will also discuss briefly the safety and ethical aspects of gene therapy and raise up some concerns that have been connected with gene therapy as a new therapeutic modality.Gene 04/2013; · 2.34 Impact Factor -
Article: Increased invasion of malignant gliomas after 15-LO-1 and HSV-tk/ganciclovir combination gene therapy.
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ABSTRACT: Recent clinical trials for malignant glioma have drawn attention to the potential therapeutic efficacy of herpes simplex virus-thymidine kinase (HSV-tk) suicide gene therapy. Nevertheless, because of the nature of these tumors, it is believed that no single treatment alone is able to combat this fatal disease. Combination therapies may provide a solution to further improve therapies against malignant gliomas. We have recently demonstrated that 15-lipoxygenase-1 (15-LO-1) is able to inhibit tumor angiogenesis as well as enhance apoptosis in tumors. As a result, we studied the potential additive/synergistic effects of 15-LO-1 gene therapy when combined with HSV-tk gene therapy for the treatment of malignant gliomas. For that, BT4C malignant glioma cells were implanted into BDIX male rats. Fourteen days after tumor cell implantation, animals were transduced using adenoviral vectors either with HSV-tk alone or in combination with 15-LO-1. The results show that the combination gene therapy neither improved inhibition of tumor growth nor did it show any benefit on survival. Instead, a profound effect on the migratory properties of the tumor cells was found, resulting in decreased survival. Similar to conventional therapies, the combination of two therapeutic genes may result in unexpected side effects, not seen when given alone.Cancer Gene Therapy advance online publication, 19 October 2012; doi:10.1038/cgt.2012.76.Cancer gene therapy 10/2012; · 3.13 Impact Factor -
Article: Targeted delivery via avidin fusion protein: Intracellular fate of biotinylated doxorubicin derivative and cellular uptake kinetics and biodistribution of biotinylated liposomes.
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ABSTRACT: In this study, avidin-biotin technology was combined with a multifunctional drug carrier modality i.e. liposomes to achieve an active and versatile targeting approach. The anti-cancer drug doxorubicin (DOX) was modified with direct biotinylation (B-DOX) (Allart et al., 2003), or encapsulated in biotinylated sterically stabilized pH-sensitive liposomes (BL-DOX), and targeted to the lentiviral vector transduced cells expressing an avidin fusion protein on the cell membrane (Lehtolainen et al., 2003; Lesch et al., 2009). The direct biotinylation of doxorubicin improved cell internalization in rat glioma (BT4C) cells expressing avidin fusion protein receptor but cell toxicity was reduced by 78-fold due to impaired nuclear localization. In contrast, liposomal formulations restored the biological activity of the DOX in several cell lines. However, mainly due to uptake via non-specific pathways the active targeting of BL-DOX was negligible in both in vitro and in vivo studies. Active targeting with multifunctional drug carrier systems is challenging and further studies will be needed to optimize the properties of targeted drug carrier and receptor expression systems.European journal of pharmaceutical sciences: official journal of the European Federation for Pharmaceutical Sciences 09/2012; · 2.61 Impact Factor -
Chapter: Gene Therapy of Glioblastoma Multiforme - Clinical Experience on the Use of Adenoviral Vectors
08/2011; , ISBN: 978-953-307-588-4 -
Article: Therapeutic delivery using gene-delivery methods.
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ABSTRACT: "With the introduction of the sophisticated tools of molecular biology, gene therapy has evolved as a new therapeutic option for different malignancies".Therapeutic delivery 04/2011; 2(4):423-6.
