通過癌癥細(xì)胞的基因組測(cè)序,，科學(xué)家們發(fā)現(xiàn)腫瘤細(xì)胞突變,，刪除或復(fù)制的大部分基因。這是個(gè)數(shù)據(jù)寶庫,，有助尋求新的藥物靶標(biāo)，但要想及時(shí)測(cè)試這些基因幾乎是不可能的,。
為了幫助加快這一進(jìn)程,，麻省理工學(xué)院的研究人員已經(jīng)開發(fā)出了RNA納米粒子，該技術(shù)能有助快速篩選新的藥物靶標(biāo),。在他們的第一項(xiàng)老鼠研究中,，Dana-Farber癌癥研究所和Broad研究院的研究人員發(fā)現(xiàn)，靶向ID4的納米粒子可以縮小卵巢腫瘤,。Sangeeta Bhatia說這項(xiàng)最新研究發(fā)表在8月15日的Science Translational Medicine雜志上,，納米粒子系統(tǒng)可以緩解癌癥藥物開發(fā)中遇到的瓶頸問題
哈佛醫(yī)學(xué)院和論文主要作者William Hahn是醫(yī)學(xué)副教授確定從國(guó)家癌癥研究所癌癥基因組測(cè)序項(xiàng)目數(shù)據(jù)庫中尋找治療癌癥有前途的新靶點(diǎn)。那些潛在的靶點(diǎn),，其中許多人認(rèn)為是不可用來開發(fā)藥物的,，蛋白質(zhì)沒有任何傳統(tǒng)藥物可以與之相結(jié)合的口袋。新的納米粒子提供短鏈RNA可以關(guān)閉特定的基因,，可能有助于科學(xué)家繞開這些不可用來開發(fā)藥物的蛋白質(zhì),。
在他們的第一次努力，研究人員決定把重點(diǎn)放在ID4基因蛋白,，因?yàn)樗诼殉材[瘤中很明顯高表達(dá),，但在其他類型的癌癥中卻并非如此。為了靶向針對(duì)ID4,，Bhatia和她的學(xué)生設(shè)計(jì)了一種新類型的RNA遞送納米顆粒,。這一新粒子可以穿透腫瘤靶向作用于ID4,，這一點(diǎn)是RNA干擾技術(shù)無法實(shí)現(xiàn)的,。在顆粒表面,，粒子都是用很短的蛋白質(zhì)片段標(biāo)記使他們能夠進(jìn)入腫瘤細(xì)胞。在小鼠卵巢腫瘤的研究中,，研究人員發(fā)現(xiàn)RNAi治療納米消除了大部分的腫瘤,。目前研究人員正在使用該顆粒測(cè)試卵巢癌以及其他類型的癌癥，包括胰臟癌其他潛在治療靶點(diǎn),，他們也在尋找到ID4基因靶向微粒作為治療卵巢癌的可能性。（生物谷：Bioon.com）
編譯自：New Nanoparticles Shrink Tumors in Mice
doi:10.1126/scitranslmed.3003778
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PMID:
Targeted Tumor-Penetrating siRNA Nanocomplexes for Credentialing the Ovarian Cancer Oncogene ID4.
Yin Ren, Hiu Wing Cheung, Geoffrey von Maltzhan, Amit Agrawal, Glenn S. Cowley, Barbara A. Weir, Jesse S. Boehm, Pablo Tamayo, Alison M. Karst, Joyce F. Liu, Michelle S. Hirsch, Jill P. Mesirov, Ronny Drapkin, David E. Root, Justin Lo, Valentina Fogal, Erkki Ruoslahti, William C. Hahn, and Sangeeta N. Bhatia.
The comprehensive characterization of a large number of cancer genomes will eventually lead to a compendium of genetic alterations in specific cancers. Unfortunately, the number and complexity of identified alterations complicate endeavors to identify biologically relevant mutations critical for tumor maintenance because many of these targets are not amenable to manipulation by small molecules or antibodies. RNA interference provides a direct way to study putative cancer targets; however, specific delivery of therapeutics to the tumor parenchyma remains an intractable problem. We describe a platform for the discovery and initial validation of cancer targets, composed of a systematic effort to identify amplified and essential genes in human cancer cell lines and tumors partnered with a novel modular delivery technology. We developed a tumor-penetrating nanocomplex (TPN) that comprised small interfering RNA (siRNA) complexed with a tandem tumor-penetrating and membrane-translocating peptide, which enabled the specific delivery of siRNA deep into the tumor parenchyma. We used TPN in vivo to evaluate inhibitor of DNA binding 4 (ID4) as a novel oncogene. Treatment of ovarian tumor–bearing mice with ID4-specific TPN suppressed growth of established tumors and significantly improved survival. These observations not only credential ID4 as an oncogene in 32% of high-grade ovarian cancers but also provide a framework for the identification, validation, and understanding of potential therapeutic cancer targets.
