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Application in biomedical research病毒的应用：病毒的应用：1）基因治疗载体；）基因治疗载体；2）免疫佐剂；免疫佐剂；3）生物实验室（载体）生物实验室（载体）作为载体的原作为载体的原因：因：1、一般、一般易制备高纯度易制备高纯度2、靶向性、靶向性/选选择性强择性强Over 2000 gene therapy trials可以去可以去 Journal of Gene Medicine网页查看进展等信息网页查看进展等信息Mainly adenovirus,retrovirus-basedChina is the only country that has approved Ad-p53 for tumor therapy(Phase IV trials)Viral vector based gene deliveryEarly stages基本都是临床早期基本都是临床早期1949,HBVThe concept to use virus treating cancer is not new.Why so little progress?Cancer Research 1949Extreme cautions need to be used when testing a viral vector for cancer therapy什么意思？什么意思？关键词：关键词：1、alphavirus M1-不一定好找，但是单不一定好找，但是单链链/双链，双链，DNA/RNA？2、Oncolytic virus3、ZAP？-提示：提示：zinc-finger antiviral protein关键词：关键词：1、alphavirus M1-天然存在的，来自中天然存在的，来自中国海南，高剂量相对安全；还能引起胶质国海南，高剂量相对安全；还能引起胶质瘤凋亡瘤凋亡(may link to oncolytic virus）关键词：关键词：oncolytic virus原理：原理：什么是什么是ZapSo easyNo need to know exact role of ZapWhich part do you not understand?Antiviral proteinFrom Wikipedia,the free encyclopediaAntiviral proteins are proteins that are induced by human or animal cells to interfere with viral replication.These proteins are isolated to inhibit the virusfrom replicating in a hosts cells and stop it from spreading to other cells.1 The Pokeweed antiviral protein and the Zinc-Finger antiviral protein are two major antiviral proteins that have undergone several tests for viruses,including HIV and influenza.Zinc-Finger Antiviral ProteineditThe Zinc-Finger Antiviral Protein(ZAP)is a specific antiviral protein that aids in the destruction of virus particles,specifically the Moloney murine leukemia virus(MLV)and the Sindbis virus(SIN).ZAP prevents the viral mRNA from building up inside the cell.5 ZAP is specifically coded for certain target mRNA.Once a correct viral mRNA is detected,it recruits an RNA exosome complex to break down and destroy the viral RNA.6 S.Miller and colleagues at theBernhard Nocht Institute for Tropical Medicine stated that:The pokeweed plant is a common plant that is often used as a dye;it is also eaten when the plant is young and tender.Studies and experiments have shown that a specific protein,the Pokeweed Antiviral Protein(PAP),could possibly be used as a thereputical use in T-cell leukemia,lymphoma,Hodgkins lymphoma,and AIDS.In an experiment posted in the Journal of Virology,mice immune systems were integrated to mimic that of humans.The mice were then infected with HIV and later given the PAP.The experiment showed that the PAP cured the mice from the HIV and with no side-effects.Due to these experiments,the U.S.Food and Drug Administration approved of using PAP on HIV patients in the U.S.,and the Medicines Control Council of South Africa approved the use for African HIV patients.Research is still being conducted with PAP to see the effectiveness on other viruses including the common cold.42002 Science中山大学中山大学PNAS2014文章图文章图1选择性选择性中山大学中山大学PNAS2014文章图文章图3筛选筛选siRNA库，发现库，发现Zap与病毒复制有关与病毒复制有关中山大学中山大学PNAS2014文章文章更多数据支持自己的假设，说明有用，好更多数据支持自己的假设，说明有用，好你的问题呢？你的问题呢？像新闻讲的一样吗？像新闻讲的一样吗？如果真是这样的，如果真是这样的，下一步做什么呢？下一步做什么呢？贵在坚持贵在坚持他们真做猴子了他们真做猴子了Cancers figure among the leading causes of morbidity and mortality worldwide.The number of new cases is expected to rise by about 70%over the next 2 decades.Development of novel therapeutic agents is urgently needed for clinical cancer therapy.Alphavirus M1 is a Getah-like virus isolated from China with a genome of positive single-strand RNA.We have previously identified that alphavirus M1 is a naturally existing oncolytic virus with significant anticancer activity against different kinds of cancer(e.g.,liver cancer,bladder cancer,and colon cancer).To support the incoming clinical trial of intravenous administration of alphavirus M1 to cancer patients,we assessed the safety of M1 in adult nonhuman primates.We previously presented the genome sequencing data of the cynomolgus macaques(Macaca fascicularis),which was demonstrated as an ideal animal species for virus infection study.Therefore,we chose cynomolgus macaques of either sex for the present safety study of oncolytic virus M1.Five experimental macaques were intravenously injected with six times of oncolytic virus M1(1109 pfu/dose)in 1 week,compared with five vehicle-injected control animals.Our results in cynomolgus macaques suggested the safety of intravenous administration of oncolytic virus M1 in cancer patients in the future（小心啊！魏什么啦）（小心啊！魏什么啦）
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