對癌癥進(jìn)行傳統(tǒng)化療中,，由于藥物作用的對象是快速分裂的細(xì)胞,，而骨髓里正常的細(xì)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(xì)胞時,，也能殺死大量正常細(xì)胞,。
美國加州理工學(xué)院應(yīng)用和計(jì)算數(shù)學(xué)系副教授奈爾斯.皮爾斯（Niles Pierce）及其同事設(shè)計(jì)了一種新方法——雜交連鎖反應(yīng)轉(zhuǎn)導(dǎo)（HCR transduction），該方法利用小RNA來程序化地識別特定癌細(xì)胞并且誘導(dǎo)其自身瓦解,，可以避免傳統(tǒng)化療所帶來的副作用,。相關(guān)論文發(fā)表在9月6日出版的美國《國家科學(xué)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(shè)計(jì)為和特殊癌細(xì)胞中突變RNA部分互補(bǔ),，以使最終能夠結(jié)合到該癌細(xì)胞的RNA上。小RNA（A）必須打開發(fā)夾結(jié)構(gòu)才能結(jié)合癌細(xì)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(jié)合。這樣形成的裸露雙鏈RNA聚合體激發(fā)了細(xì)胞中蛋白激酶R（PKR）主導(dǎo)的天然抗病毒免疫反應(yīng),，誘導(dǎo)細(xì)胞凋亡程序,，從而清除癌細(xì)胞。
皮爾斯在三種類型的癌（膠質(zhì)母細(xì)胞瘤,，前列腺癌和尤文氏肉瘤）細(xì)胞中進(jìn)行試驗(yàn),，結(jié)果使癌細(xì)胞數(shù)量成20-100倍下降。然而,，皮爾斯說,，條件性小RNA治療能否應(yīng)用于病人身上還需繼續(xù)研究。（科學(xué)網(wǎng) 任春曉/編譯）（生物谷Bioon.com）
生物谷近期特別推薦會議：
2010細(xì)胞治療研究進(jìn)展與臨床應(yīng)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(chǔ)和轉(zhuǎn)化醫(yī)學(xué)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.
