瑞典研究人員最新發(fā)現(xiàn),,一種番茄基因與藥物組合后能破壞癌細(xì)胞,,這一發(fā)現(xiàn)將有助于用基因療法治療癌癥,。
瑞典隆德大學(xué)研究人員日前發(fā)表公報說,,這種番茄基因在幫助建立和修復(fù)番茄基因組方面“非?;钴S”,,但它本身并不足以破壞癌細(xì)胞,。在先后測試了不同藥物后,研究人員最終發(fā)現(xiàn),,這種番茄基因與抗艾滋病藥物AZT組合后,,能更有效地打擊癌細(xì)胞。
研究人員指出,,很多人對基因療法心存疑慮,,擔(dān)心病人的基因在接受治療后發(fā)生改變,引發(fā)更多的不良反應(yīng),。然而,,上述研究并不存在這種風(fēng)險,因?yàn)榉鸦騼H僅被注入癌細(xì)胞內(nèi),,并不影響其他細(xì)胞,。(生物谷Bioon.com)
更多閱讀
Science:基因治療可有效減緩腦部疾病發(fā)展
NEJM:利用基因治療失明獲得成功
Nature Genetics:大紅番茄突變造
JBC:香蕉或成抗艾滋利器
生物谷推薦原文出處:
Neuro Oncol. 2010 Feb 13 PMID: 20154339
Plant thymidine kinase 1: a novel efficient suicide gene for malignant glioma therapy.
Khan Z, Knecht W, Willer M, Rozpedowska E, Kristoffersen P, Clausen AR, Munch-Petersen B, Almqvist PM, Gojkovic Z, Piskur J, Ekstr?m TJ.
Department of Clinical Neuroscience, Karolinska Institutet, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden (Z.K., P.M.A., T.J.E.); BioCentrum-DTU, Technical University of Denmark, Denmark (W.K., J.P.); ZGene A/S, H?rsholm, Denmark (M.W., P.K., Z.G.); Cell and Organism Biology, Lund University, Lund, Sweden (E.R., A.R.C., J.P.); Science, Systems and Models, Roskilde University, Roskilde, Denmark (B.M.-P.).
The prognosis for malignant gliomas remains poor, and new treatments are urgently needed. Targeted suicide gene therapy exploits the enzymatic conversion of a prodrug, such as a nucleoside analog, into a cytotoxic compound. Although this therapeutic strategy has been considered a promising regimen for central nervous system (CNS) tumors, several obstacles have been encountered such as inefficient gene transfer to the tumor cells, limited prodrug penetration into the CNS, and inefficient enzymatic activity of the suicide gene. We report here the cloning and successful application of a novel thymidine kinase 1 (TK1) from the tomato plant, with favorable characteristics in vitro and in vivo. This enzyme (toTK1) is highly specific for the nucleoside analog prodrug zidovudine (azidothymidine, AZT), which is known to penetrate the blood-brain barrier. An important feature of toTK1 is that it efficiently phosphorylates its substrate AZT not only to AZT monophosphate, but also to AZT diphosphate, with excellent kinetics. The efficiency of the toTK1/AZT system was confirmed when toTK1-transduced human glioblastoma (GBM) cells displayed a 500-fold increased sensitivity to AZT compared with wild-type cells. In addition, when neural progenitor cells were used as delivery vectors for toTK1 in intracranial GBM xenografts in nude rats, substantial attenuation of tumor growth was achieved in animals exposed to AZT, and survival of the animals was significantly improved compared with controls. The novel toTK1/AZT suicide gene therapy system in combination with stem cell-mediated gene delivery promises new treatment of malignant gliomas.