美國加州理工學(xué)院等機構(gòu)的研究人員報告說,，他們合成了一種直徑僅為70納米的微小載體。這種攜帶了特定RNA的載體進入血液后,，不會引起免疫系統(tǒng)的排異反應(yīng),，可隨著血液流動到達發(fā)生癌變的部位，然后進入癌細胞釋放出RNA,，而剩下的載體物質(zhì)由于太過微小可隨著尿液排出,。
該研究發(fā)表于3月21日 英國《自然》雜志網(wǎng)站研究報告上，美國研究人員成功利用納米級別的微小載體將特定的RNA（核糖核酸）送達人體癌變部位,，從而干擾了癌細胞的基因并起到治療作用,。
RNA是基因指導(dǎo)合成蛋白質(zhì)的過程中所必需的工具，這段人為添加的RNA可以干擾癌細胞中原有RNA的作用,，使其不能合成相應(yīng)的蛋白質(zhì),。在試驗中，研究人員對患有皮膚癌的病人使用了這項新技術(shù),，結(jié)果發(fā)現(xiàn)它可以精確阻礙名為RRM2的目標(biāo)基因發(fā)揮作用,，使得患者癌細胞中相應(yīng)的蛋白質(zhì)減少，從而起到治療癌癥的作用,。
研究人員馬克·戴維斯說,，通過選擇所使用的RNA，這項技術(shù)可以阻礙任何基因發(fā)揮作用,，因此有望用于廣泛治療各種癌癥,。
這是首次實現(xiàn)在人體中利用RNA干擾來治療癌癥的研究。外加RNA可以阻止特定基因發(fā)揮作用的現(xiàn)象稱為“RNA干擾”,，由安德魯·法爾和克雷格·梅洛在上世紀(jì)90年代發(fā)現(xiàn),，他們因此榮獲2006年諾貝爾生理學(xué)或醫(yī)學(xué)獎。（生物谷Bioon.com）
生物谷推薦原文出處：
Nature doi:10.1038/nature08956
Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles
Mark E. Davis1, Jonathan E. Zuckerman1, Chung Hang J. Choi1, David Seligson2,3, Anthony Tolcher5, Christopher A. Alabi1,8, Yun Yen6, Jeremy D. Heidel7 & Antoni Ribas2,4
Chemical Engineering, California Institute of Technology, Pasadena, California 91125, USA
Jonsson Comprehensive Cancer Center,
Department of Pathology, David Geffen School of Medicine,
Department of Medicine, Division of Hematology Oncology, David Geffen School of Medicine, University of California, Los Angeles, California 90095, USA
START - South Texas Accelerated Research Therapeutics, LLC, 4383 Medical Drive, 4th Floor, San Antonio, Texas 78229, USA
Department of Medical Oncology and Therapeutics Research, City of Hope Comprehensive Cancer Center, 1500 E. Duarte Road, Duarte, California 91010, USA
Calando Pharmaceuticals, 201 South Lake Avenue, Suite 703, Pasadena, California 91101, USA
Present address: Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.
Therapeutics that are designed to engage RNA interference (RNAi) pathways have the potential to provide new, major ways of imparting therapy to patients1, 2. Long, double-stranded RNAs were first shown to mediate RNAi in Caenorhabditis elegans 3, and the potential use of RNAi for human therapy has been demonstrated by the finding that small interfering RNAs (siRNAs; approximately 21-base-pair double-stranded RNA) can elicit RNAi in mammalian cells without producing an interferon response4. We are at present conducting the first in-human phase I clinical trial involving the systemic administration of siRNA to patients with solid cancers using a targeted, nanoparticle delivery system. Here we provide evidence of inducing an RNAi mechanism of action in a human from the delivered siRNA. Tumour biopsies from melanoma patients obtained after treatment show the presence of intracellularly localized nanoparticles in amounts that correlate with dose levels of the nanoparticles administered (this is, to our knowledge, a first for systemically delivered nanoparticles of any kind). Furthermore, a reduction was found in both the specific messenger RNA (M2 subunit of ribonucleotide reductase (RRM2)) and the protein (RRM2) levels when compared to pre-dosing tissue. Most notably, we detect the presence of an mRNA fragment that demonstrates that siRNA-mediated mRNA cleavage occurs specifically at the site predicted for an RNAi mechanism from a patient who received the highest dose of the nanoparticles. Together, these data demonstrate that siRNA administered systemically to a human can produce a specific gene inhibition (reduction in mRNA and protein) by an RNAi mechanism of action.
