抑制肿瘤发展——磁共振扫描显示，运用ALN-VSP疗法，肝脏肿瘤中的血流量[红色]在下降，而此种疗法可阻止癌细胞产生构成血管的蛋白质。

Since last April, 19 cancer patients whose liver tumors hadn’t responded to chemotherapy have taken an experimental drug. Within weeks of the first dose, it appeared to work, by preventing tumors from making proteins they need to survive. The results are preliminary yet encouraging. With a slight redesign, the drug might work for hundreds of diseases, fulfilling the promise that wonder cures like stem cells and gene therapy have failed to deliver.

       自从去年四月，19名未接受过化疗的肝癌病人已经服用了试验性的药品。在第一次服用后的数周内，通过阻止肿瘤形成内部所需的蛋白质，药效似乎有所显现。初步得到的结果还算令人鼓舞。稍作改动，药品也许对治疗数百种疾病有效，以此兑现诸如实现干细胞和基因治疗这些神奇疗法的承诺。3

The biotech company Alnylam announced in June that its drug ALN-VSP cut off blood flow to 62 percent of liver-cancer tumors in those 19 patients, by triggering a rarely used defense mechanism in the body to silence cancerous genes. Whereas conventional drugs stop disease-causing proteins, ALN-VSP uses RNA interference (RNAi) therapy to stop cells from making proteins in the first place, a tactic that could work for just about any disease. “Imagine that your kitchen floods,” says biochemist and Alnylam CEO John Maraganore. “Today’s medicines mop it up. RNAi technology turns off the faucet.”

        生物技术企业奥尼兰姆（Alnylam）六月宣布，通过触发体内鲜有使用的防御机制让癌症基因沉默，其新药ALN-VSP可阻断19名病患肝部恶性肿瘤中62%的血流量。然而与传统药物阻断致病蛋白质不同，ALN-VSP运用RNA干扰（RNAi）疗法来阻断癌细胞在原来的部位产生蛋白质，这是一种几乎可针对任何疾病的普适疗法。“想象你的厨房水流一地，”生物化学家、奥尼兰姆执行总裁John Maraganore说，“当今的药物可将这些水吸干，RNA干扰技术相当于为你关上了水龙头。”2

Here’s another analogy: If DNA is the blueprint for proteins, RNA is the contractor. It makes single-stranded copies of DNA’s genes, called mRNA, which tell the cell to produce proteins. In 1998, scientists identified RNAi, a mechanism that primitive organisms use to detect and destroy virus’s double-stranded RNA and any viral mRNA. Mammals’ immune systems made RNAi’s antiviral function irrelevant (although all vertebrates, including humans, still use RNAi to regulate mRNA activity), but researchers found that introducing small segments of double-stranded RNA to cells could trigger the ancient mechanism and selectively halt the production of specific proteins.

       这里还有另一个类比：如果DNA对蛋白质来说是远景，那RNA就是纽带。它可促使DNA基因单链复制，这被称作信使RNA（mRNA），它会传递信息给细胞产生蛋白质。1998年，科学家发现了RNAi，这是一种原始生物用来检测和摧毁病毒的双链RNA和任何携带病毒的mRNA的机制。（尽管包括人类在内的所有的脊椎动物，一直使用RNAi来调节mRNA活动），哺乳动物的免疫系统和RNAi抗病毒作用无关，但研究人员已经发现，将一小部分双链RNA片段引入细胞也许可以触发这一古老机制，并选择性的停止特定蛋白质的产生。4

That ability makes RNAi a potential fix for many diseases, including cancer, that arise when abnormal cells produce excessive amounts of everyday proteins. In theory, manipulating RNAi to kill proteins is simple. ALN-VSP, for example, consists of synthetic double-stranded RNA designed to match tumor mRNA that codes for two proteins: VEGF, which cancers overproduce to help grow new blood vessels, and KSP, which sets off rapid cell division. The researchers send the synthetic RNA into liver cells, and the body’s RNAi system kills both the synthetic RNA and any matching tumor-grown mRNA. Knock out the mRNAs coding for those proteins—which in the liver are produced only by cancer cells—and the tumor stops growing.

       上述的这种能力使RNAi具有一种针对包括癌症在内的许多疾病的潜在修复能力，而这些疾病常常是由病变细胞产生过量的日常蛋白质所致。这一理论中，操控RNAi来杀死蛋白质并不难。例如，ALN-VSP是由合成双链RNA组成，设计出来与肿瘤中用于编码两种蛋白质的mRNA相匹配：血管内皮生长因子（VEGF），其肿瘤过度增殖会帮助新血管的生长；纺锤体驱动蛋白（KSP），可引起快速细胞分裂。研究人员将合成RNA注入肝细胞内，体内的RNAi系统便会杀死合成RNA以及任何与之匹配的与肿瘤生长相关的信使RNA。阻止编码肝脏中仅通过癌细胞产生蛋白质的信使RNA，肿瘤便相继停止生长。3

“We can turn off any one of 20,000 genes with RNAi,” says Bruce Sullenger, a molecular biologist researching RNAi at Duke University. “The challenge has been to get a drug into only the desired cells and not harm others.” Researchers have worried that a drug might disrupt normal protein production in a healthy cell, or that the immune system will destroy the drug before it reaches its target.                                                                                                                                                                                                                                                                                                                                                                                                                     

Alnylam overcame both concerns by packaging the drug in a fatty envelope that is absorbed primarily by the liver. This allowed doctors to administer the drug through the blood, rather than by an injection to one spot, which improves results by ensuring that the entire liver receives an even dose.

       “我们可以关闭与RNAi相关的两万个基因中任何一个，”来自杜克大学研究RNAi的分子生物学家Burce Sullenger说，“挑战已经出现，便是使药物只进入我们所期望的细胞中，而不伤及其他正常细胞。”研究人员担心，药物也许会破坏健康细胞中正常蛋白质产生，或是在其到达靶细胞之前，被免疫系统摧毁。

       奥尼兰姆克服这两点，他们将药物包在脂肪薄层里，便可达到主要被肝脏吸收的效果。这允许医生从血管注射药物，而不是通过一点上的注射，这可改善药物的效果，确保整个肝脏都能接收到均等的剂量。

The technique’s ability to attack single genes could lead to drugs for the 75 percent of cancer genes that lack any specific treatment, as well as for other illnesses. Alnylam is already testing RNAi therapy for Huntington’s disease and high cholesterol in cell cultures; other researchers are tackling macular degeneration, muscular dystrophy and HIV. The potential has driven nearly every major pharmaceutical company to start an RNAi program.

       这项能攻击单个基因的技术也许会催生应对75%的缺乏任何特殊疗法癌症基因的药物，还包括其他的疾病。奥尼兰姆已经针对细胞培养的亨廷顿氏病和高水品胆固醇进行了RNAi疗法测试；另一些研究人员正在研究解决黄斑变性、肌肉萎缩和艾滋病病毒。潜在的应用已经驱使几乎每一个主要的制药公司开展RNAi计划。 

Because the approach is fundamentally simple, RNAi therapy could be ready within two years, say experts including John Rossi, a molecular geneticist at City of Hope National Medical Center in California. Alnylam plans to enroll an additional 36 patients in the ALN-VSP trial and increase the dosage, but the early results are good enough to suggest that it could be among the first RNAi therapies to hit the market. “I think RNAi could work for anything,” Rossi says. “But even if it only works for liver cancer, it would be pretty good.” For liver-cancer patients who have been failed by chemotherapy and radiation and felt their harsh side effects, that would be wonder drug enough.

       因为此方法原理简单，RNAi疗法可能在今后两年内日臻完善，包括加利福尼亚希望之城医疗中心的分子遗传学家约翰·罗西在内的专家们如此表示。奥尼兰姆计划再对36名其他的病人展开新药测试，增加药物用量，但早期的结果相当好，也表明了它可能成为第一批投放市场的RNAi疗法治疗药。“我认为RNAi对所有的病都有效，”罗西说，“但即使它只对肝癌有效，那也已经非常棒了。”对于那些饱受化疗和辐射巨大副作用、却不能治愈肝癌的患者来说，这绝对是灵丹妙药。