Nat Commun:科学家开发出专杀肿瘤的神奇病毒

2017-03-23 煎蛋 福建新闻网

近日来自 IDIBAPS 生物医学研究所以及巴塞罗纳生物医学研究协会 ( IRB Barcelona ) 的科学家们在 Nature Communications 上联合发表一项关于肿瘤治疗方面的重大成果。研究称他们使用新方式对病毒的基因进行修饰,从而将其改造成专门消灭肿瘤细胞的神奇病毒。传统的肿瘤治疗由于选择性较差往往会引起各种不良反应,因此新型肿瘤疗法开发最重要的一点就是在不伤害正常细胞的基础

近日来自 IDIBAPS 生物医学研究所以及巴塞罗纳生物医学研究协会 ( IRB Barcelona ) 的科学家们在 Nature Communications 上联合发表一项关于肿瘤治疗方面的重大成果。研究称他们使用新方式对病毒的基因进行修饰,从而将其改造成专门消灭肿瘤细胞的神奇病毒。

传统的肿瘤治疗由于选择性较差往往会引起各种不良反应,因此新型肿瘤疗法开发最重要的一点就是在不伤害正常细胞的基础上消灭癌细胞。在众多新型肿瘤疗法中有一类基于溶瘤病毒开发的疗法——通过基因修饰让病毒感染肿瘤细胞。近年来多个研究团队专注于该疗法,希望借助基因工程等方法开发出更为有效的抗肿瘤病毒。不过随着抗肿瘤效果的增加,往往对正常细胞的伤害也就越大,它的毒性也随之增大。如何尽可能的降低对正常细胞的影响,是新型疗法开发的关键。

IDIBAPS 和 IRB Barcelona 学者们在文章里称他们开发出新型方法能让腺病毒对肿瘤细胞具有高度特异性。 IRB Barcelona 的一名研究者 Raúl Méndez 解释说:"我们主要利用了 CPEBs 类蛋白在正常和肿瘤组织中的表达的差异性。" CPEB 家族主要由四种蛋白组成,是一类 RNA 结合蛋白。在正常状态下,它们能够控制数百中基因的表达以维持身体的正常机能以及组织的自我修复能力。而一旦 CPEBs 蛋白失衡,它们会改变细胞内基因的表达,为病变 ( 比如癌症 ) 添砖加瓦。"我们尤其关注两类 CPEB 蛋白失衡:一类是 CPEB4, 在此前的研究中我们已经证明该类蛋白在肿瘤细胞高表达,是肿瘤组织快速生长所必须的;另一类是 CPEB1,在正常细胞高度表达,而在肿瘤细胞中却几乎不表达。我们开发的病毒具有双重识别功能,只攻击那些 CPEB4 高表达和 CPEB1 低表达的细胞,这样就会避免伤害正常组织",Méndez 说。

"在研究中我们选择了腺病毒,该病毒能够感染呼吸道、尿道、胃肠道以及眼部,它同时具有一些特别适宜用来消灭肿瘤的特性",Cristina Fillat 解释说。不过在使用它们消灭肿瘤之前,必须对病毒基因组进行修饰。本研究中研究者们在病毒控制的核心区插入了一段序列使病毒能够识别 CPEB 蛋白,在体外实验中该病毒对胰腺肿瘤细胞具有较高活性,而在动物模型实验中明显抑制了小鼠肿瘤的生长。该研究中开发的抗肿瘤病毒相当复杂,它既会被 CPEB4 激活也会被 CPEB1 抑制。因此,在 CPEB1 高表达的正常细胞中该病毒的会被减毒,而在 CPEB4 高表达的肿瘤中会维持甚至增强该病毒的毒性。"当病毒进入到肿瘤细胞内会不断的自我复制,待该细胞破裂后释放更多的病毒微粒进而感染更多的肿瘤细胞," Fillat 说。她补充到:"这个新型疗法相当有趣,它具有高度的肿瘤细胞选择性。"

由于 CPEB4 蛋白在多种肿瘤细胞中高度表达,因此该类高度肿瘤特异性行疗法可能对其他实体瘤也有效果 . 研究者们正在努力将该疗法与现有的一些临床疗法或者正在开发一些方法相结合,以期达到更好的治疗效果。

原始出处:

Villanueva E, Navarro P, Rovira-Rigau M,et al. Translational reprogramming in tumour cells can generate oncoselectivity in viral therapies. Nat Commun. 2017 Mar 16.

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    2017-09-24 liuli5079
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    2017-07-30 liye789132251
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    2017-03-24 ann y

    :科学家开发出专杀肿瘤

    0

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    2017-03-24 1dd8c52fm63(暂无匿称)

    继续关注

    0

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    2017-03-24 飛歌

    学习了很有用

    0

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    2017-03-23 依way

    如果真的能用于临床就好了

    0

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