新基因治疗在小鼠中收缩积极的肿瘤

StephenW

                        New Gene Therapy Shrinks Aggressive Tumors in Mice        

Scientists shut down cancer-causing fusion genes with CRISPR.

      

                                By Aggie Mika  | May 2, 2017                       

                                       
                                       
                                                                                                                   PIXABAY, TYPOGRAPHYIMAGES

        A CRISPR-based gene therapy that targets cancerous fusion genes—hybrid genes that are formed when two previously distinct genes join together—shrinks aggressive forms of liver and prostate cancers in mice.
        The approach could be developed to address the problem of drug resistance. Cancer cells are prone to evolving new mutations when treated with traditional chemotherapy; using genome editing, the new mutations could be targeted to continue fighting the disease, Jian-Hua Luo, the lead author and a professor of pathology at the University of Pittsburgh School of Medicine, said in a press release.
        In the study, published Monday (May 1) in Nature Biotechnology,  Luo and colleagues set their sights on two fusions genes they had previously found to be associated with prostate cancer and various forms of rapid and invasive cancer, including liver tumors. Using a modified CRISPR-Cas9 tool that creates a single- rather than double-stranded break in DNA, they targeted the chromosomal breakpoints that form these fusion genes and replaced fusion DNA with a gene encoding the enzyme HSV1-tk.
        This enzyme effectively kills tumor cells by converting the drug ganciclovir into its active form, which then blocks DNA synthesis and leads to cell death. (Ganciclovir is used to treat cytomegalovirus in humans.)
        The researchers found that HSV1-tk insertion followed by ganciclovir treatment killed tumors in dishes and shrank them in mice. In mice transplanted with human prostate and liver cancers, this gene therapy also stopped tumors from spreading, and allowed all 17 mice to survive the eight-week study. On the other hand, tumors continued to grow and spread in control mice, and all died before the study ended.
        “This is the first time that gene editing has been used to specifically target cancer fusion genes,” said Luo in the statement. “It is really exciting because it lays the groundwork for what could become a totally new approach to treating cancer.”
                                       
                                                                        Tags                                preclinical,                                 nickase,                                 gene therapy,                                 fusion gene,                                 CRISPR/Cas and                                 cancer research                       
                                       

StephenW

新基因治疗在小鼠中收缩积极的肿瘤

科学家用CRISPR关闭致癌融合基因。

作者：Aggie Mika | 2017年5月2日

PIXABAY，TYPOGRAPHYIMAGES



基于CRISPR的基因治疗靶向癌性融合基因 - 当两个以前不同的基因连接在一起时形成的杂交基因 - 缩小了小鼠肝脏和前列腺癌的侵袭性形式。

该方法可以用来解决耐药性问题。当用传统化学疗法治疗时，癌细胞易发生新的突变;匹兹堡大学医学院病理学教授罗建华在新闻发布会上表示，利用基因组编辑，新突变可能成为继续抗病的对象。

在自然生物技术周一（5月1日）发表的研究中，罗和他的同事们将目光投向了以前发现与前列腺癌和各种形式的快速和侵袭性癌症（包括肝肿瘤）相关的两个融合基因。使用修饰的CRISPR-Cas9工具，其在DNA中产生单一而不是双链断裂，它们靶向形成这些融合基因的染色体断裂点，并用编码HSV1-tk的基因替换融合DNA。

该酶通过将更昔洛韦药物转化为其活性形式有效地杀死肿瘤细胞，其阻断DNA合成并导致细胞死亡。 （更昔洛韦用于治疗人类巨细胞病毒）

研究人员发现，HSV1-tk插入随后更昔洛韦治疗杀死了菜肴中的肿瘤，并在小鼠中收缩。在移植人类前列腺癌和肝癌的小鼠中，这种基因治疗也阻止了肿瘤扩散，并允许所有17只小鼠在8周的研究中生存。另一方面，肿瘤在对照小鼠中继续生长并扩散，并且在研究结束之前都死亡。

罗恩在声明中说：“这是基因编辑第一次用于特异性靶向癌症融合基因。 “这真是令人兴奋，因为它为可能成为治疗癌症的全新方法奠定了基础。”
标签
临床前，切口酶，基因治疗，融合基因，CRISPR / Cas和癌症研究

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