對癌癥進行傳統(tǒng)化療中,由于藥物作用的對象是快速分裂的細胞,,而骨髓里正常的細胞也具有快速分裂的特性,因此藥物在殺死快速分裂的癌細胞時,,也能殺死大量正常細胞,。
美國加州理工學院應用和計算數學系副教授奈爾斯.皮爾斯(Niles Pierce)及其同事設計了一種新方法——雜交連鎖反應轉導(HCR transduction),該方法利用小RNA來程序化地識別特定癌細胞并且誘導其自身瓦解,,可以避免傳統(tǒng)化療所帶來的副作用,。相關論文發(fā)表在9月6日出版的美國《國家科學院院刊》(PNAS)上。
該方法利用了兩種不同類的條件性小RNA(比如:A和B),。其中一個小RNA(A)設計為和特殊癌細胞中突變RNA部分互補,,以使最終能夠結合到該癌細胞的RNA上。小RNA(A)必須打開發(fā)夾結構才能結合癌細胞RNA上,,同時,,打開發(fā)夾的小RNA(A)也能夠自然地與另一個打開發(fā)夾小RNA(B)結合,。這樣形成的裸露雙鏈RNA聚合體激發(fā)了細胞中蛋白激酶R(PKR)主導的天然抗病毒免疫反應,誘導細胞凋亡程序,,從而清除癌細胞,。
皮爾斯在三種類型的癌(膠質母細胞瘤,前列腺癌和尤文氏肉瘤)細胞中進行試驗,,結果使癌細胞數量成20-100倍下降,。然而,皮爾斯說,,條件性小RNA治療能否應用于病人身上還需繼續(xù)研究,。(科學網 任春曉/編譯)(生物谷Bioon.com)
生物谷近期特別推薦會議:
2010細胞治療研究進展與臨床應用前沿研討會 www.Cell-therapies.net 2010年9月23日-25日天津召開
第一屆腫瘤基礎和轉化醫(yī)學國際研討會 www.cancerasia.org 2010年10月12日-10月15日上海召開
生物谷推薦英文摘要:
PNAS doi: 10.1073/pnas.1006377107
Selective cell death mediated by small conditional RNAs
Suvir Venkataramana, Robert M. Dirksa,b, Christine T. Uedab, and Niles A. Piercea,c,1
aDepartment of Bioengineering;
bDepartment of Chemistry; and
cDepartment of Applied and Computational Mathematics, California Institute of Technology, Pasadena, CA 91125
Cancer cells are characterized by genetic mutations that deregulate cell proliferation and suppress cell death. To arrest the uncontrolled replication of malignant cells, conventional chemotherapies systemically disrupt cell division, causing diverse and often severe side effects as a result of collateral damage to normal cells. Seeking to address this shortcoming, we pursue therapeutic regulation that is conditional, activating selectively in cancer cells. This functionality is achieved using small conditional RNAs that interact and change conformation to mechanically transduce between detection of a cancer mutation and activation of a therapeutic pathway. Here, we describe small conditional RNAs that undergo hybridization chain reactions (HCR) to induce cell death via an innate immune response if and only if a cognate mRNA cancer marker is detected within a cell. The sequences of the small conditional RNAs can be designed to accept different mRNA markers as inputs to HCR transduction, providing a programmable framework for selective killing of diverse cancer cells. In cultured human cancer cells (glioblastoma, prostate carcinoma, Ewing’s sarcoma), HCR transduction mediates cell death with striking efficacy and selectivity, yielding a 20- to 100-fold reduction in population for cells containing a cognate marker, and no measurable reduction otherwise. Our results indicate that programmable mechanical transduction with small conditional RNAs represents a fundamental principle for exploring therapeutic conditional regulation in living cells.