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标题: 病毒治疗癌症！？ [打印本页]

作者: ipsvirus 时间: 2015-3-4 11:01
标题: 病毒治疗癌症！？

近日，国际生物学期刊Cell Research在线刊登了美国南加州大学研究人员的一项最新研究成果，他们应用植物miRNA能够被哺乳动物消化道细胞消化吸收，进入组织发挥基因调控这一发现，开发了一种口服miRNA混合剂给药系统，并通过动物实验证明口服肿瘤抑制性miRNA能够有效抑制肿瘤生长。

miRNA是一类小的非编码RNA，几乎存在于所有真核生物中，并在调控基因表达方面发挥重要作用。在人类所有蛋白质编码基因中，约有60%的基因会受到miRNA调控，机体几乎每一个生理过程都会受到miRNA的影响。同时也有许多疾病与miRNA失调相关。之前研究发现在肿瘤细胞中，一类特定的作为肿瘤抑制因子的miRNA其表达受到下调，恢复这类miRNA表达能够抑制动物模型肿瘤发生。因此如何上调这类miRNA使其发挥肿瘤抑制因子作用越来越得到人们的广泛关注。

研究人员发现来自于食物的植物miRNAs能够被哺乳动物消化道细胞吸收，并被包装成微泡转运进入血液，并被输送到各个组织，调控基因表达。因此研究人员借助于这一发现开发了一种有效的给药系统，他们将多种肿瘤抑制因子miRNAs的混合剂以口服形式处理结肠癌小鼠模型，结果发现小鼠肿瘤负荷减少，并且在实验期间均保持健康和正常的体重增加，没有明显毒性。结果表明用肿瘤抑制性miRNA模拟植物小RNA即可通过口服的形式给与结肠癌小鼠模型并发挥肿瘤抑制功能，减小肿瘤负荷。

A novel chemopreventive strategy based on therapeutic microRNAs produced in plants
Sizolwenkosi Mlotshwa1,*, Gail J Pruss1,*, John L MacArthur1, Matthew W Endres1, Celestia Davis1, Lorne J Hofseth2, Maria Marjorette Pe?a1 and Vicki Vance1
MicroRNAs (miRNAs) are small non-coding RNAs that play a critical role in regulation of gene expression in nearly all eukaryotic organisms, including mammals. In humans, an estimated 60% of all protein-coding genes are targeted by miRNAs, affecting virtually every physiological process in the body1. In addition, a diverse array of human diseases is associated with dysregulation of miRNAs2. In many forms of cancer, for example, certain miRNAs, termed tumor suppressor miRNAs, are downregulated in diseased cells. Restoration of the downregulated tumor suppressor miRNA has been shown to block one or more steps in oncogenesis in animal models and cell culture systems. Thus, the therapeutic potential of tumor suppressor miRNAs has been experimentally confirmed and is now widely recognized. However, systemic delivery of such therapeutic small RNAs in humans is challenging and numerous delivery options are currently under investigation.
转自http://news.bioon.com/article/6666327.html

那是否也可以用病毒作为载体，将miRNA，siRNA等控制肿瘤的生长。最近CRISPR技术非常火，用于基因编辑功能非常强大，是否也可以开发出用病毒载体将CRISPR系统导入肿瘤细胞，针对原癌基因或者抑癌基因的编辑？欢迎大家补充

作者: cao1976 时间: 2015-3-4 11:27
很受启发，感谢楼主分享！

作者: ipsvirus 时间: 2015-3-4 19:28
Nature Medicine有篇文章报道了通过CRISPR系统在分离的人体正常肠道组织细胞中引入了肿瘤抑制基因APC、SMAD4和TP53突变，以及原癌基因KRAS和PIK3CA突变，使得这些组织细胞能够不依赖干细胞因子就能在体外生长，而且移植到小鼠肾包膜下会形成肿瘤。

Modeling colorectal cancer using CRISPR-Cas9–mediated engineering of human intestinal organoids
Human colorectal tumors bear recurrent mutations in genes encoding proteins operative in the WNT, MAPK, TGF-β, TP53 and PI3K pathways1, 2. Although these pathways influence intestinal stem cell niche signaling3, 4, 5, the extent to which mutations in these pathways contribute to human colorectal carcinogenesis remains unclear. Here we use the CRISPR-Cas9 genome-editing system6, 7 to introduce multiple such mutations into organoids derived from normal human intestinal epithelium. By modulating the culture conditions to mimic that of the intestinal niche, we selected isogenic organoids harboring mutations in the tumor suppressor genes APC, SMAD4 and TP53, and in the oncogenes KRAS and/or PIK3CA. Organoids engineered to express all five mutations grew independently of niche factors in vitro, and they formed tumors after implantation under the kidney subcapsule in mice. Although they formed micrometastases containing dormant tumor-initiating cells after injection into the spleen of mice, they failed to colonize in the liver. In contrast, engineered organoids derived from chromosome-instable human adenomas formed macrometastatic colonies. These results suggest that 'driver' pathway mutations enable stem cell maintenance in the hostile tumor microenvironment, but that additional molecular lesions are required for invasive behavior.

这篇文章相当于在体外通过对一些基因进行突变，模拟了肠癌细胞的发生。那么放过来想通过组织特异性病毒将CRISPR的组件Cas9和guide RNA引入到癌细胞中对一些突变基因进行恢复突变是否能起到治疗癌症的效果！？

作者: biovirus 时间: 2015-3-5 15:50
学习了！食物中有抗癌的，会不会也有致癌的？

作者: ipsvirus 时间: 2015-3-6 17:46

biovirus 发表于 2015-3-5 15:50
学习了！食物中有抗癌的，会不会也有致癌的？

我觉得不可避免的会有，这也是目前转基因食品被广泛抵制的原因

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