Muramatsu Naomi, Ichikawa Misa, Katagiri Tomoko, Taguchi Yumi, Hatanaka Takashi, Okuda Tomoyuki, Okamoto Hirokazu
Randis Medical Developments Inc., Nagoya, Aichi, Japan.
Department of Drug Delivery Research, Faculty of Pharmacy, Meijo University, Nagoya, Aichi, Japan.
Gene Ther. 2024 Mar;31(3-4):119-127. doi: 10.1038/s41434-023-00424-y. Epub 2023 Oct 13.
Dry gene powder is a novel non-viral gene-delivery system, which is inhalable with high gene expression. Previously, we showed that the transfection of p16 or TP53 by dry gene powder resulted in growth inhibitions of lung cancer and malignant pleural mesothelioma (MPM) in vitro and in vivo. Here, we report that dry gene powder containing p53- expression-plasmid DNA enhanced the therapeutic effects of cisplatin (CDDP) against MPM even in the presence of endogenous p53. Furthermore, our results indicated that the safe transfection with a higher plasmid DNA (pDNA) concentration suppressed MPM growth independently of chemotherapeutic agents. To develop a new therapeutic alternative for MPM patients without safety concerns over "vector doses", our in vitro data provide basic understandings for dry gene powder.
干粉基因是一种新型的非病毒基因递送系统，具有可吸入性且基因表达水平高。此前，我们发现通过干粉基因转染p16或TP53可在体外和体内抑制肺癌和恶性胸膜间皮瘤（MPM）的生长。在此，我们报告，即使在内源性p53存在的情况下，含p53表达质粒DNA的干粉基因也能增强顺铂（CDDP）对MPM的治疗效果。此外，我们的结果表明，以较高质粒DNA（pDNA）浓度进行安全转染可独立于化疗药物抑制MPM生长。为了开发一种对MPM患者无“载体剂量”安全担忧的新治疗方案，我们的体外数据为干粉基因提供了基本认识。
