研发动态

我国在生物技术的部分领域已处于世界前列科技部近日表示,“十五”期间是我国生物技术与产业发展的最快时期,国家科技投入增长了近4倍,进入临床药物数量增长了8倍,专利申请数增长10倍。我国在基因组学、蛋白组学、SARS疫苗研究等一些技术领域已经进入世界前列,许多生物技术产品     

我国生物技术的研究进展

20世纪70年代以来,由于DNA重组和转基因技术等一系列现代生物技术的建立,生物技术已成为当今世界发展最快、最活跃的高新技术领域之一。目前,生物技术已在农业、医药、轻工、食品、环保、海洋和能源等方面得到应用,并在医药、农业等领域取得重大突破,其成果的转化和利用对上述行业的技术更新和产品换代发挥着越来越重要的作用,医药生物技术的新型产业正在形成。世界各国尤其是发达国家纷纷把生物技术作为21世纪的关键技术给予高度重视和支持,以增强本国的实力和国际竞争力。现就我国生物技术的发展趋势综述如下。1我国生物技术领域取得的…     

刍议重症急性呼吸综合征带来的启示

重症急性呼吸综合征(SARS)自暴发至今,已经造成数百人死亡、数百亿美元的经济损失。在同SARS斗争的同时,应该想到生物技术发展对人类产生的双重效应,以及如何防止生物科学新突破被误用和滥用;也应该想到生物恐怖对人类可能的威胁,因此应积极保护我们的基因资源。SARS除了带给人类灾难以外,也带给我们更多的思考,并可能会促成我们建立相应的机制,以应对未来可能出现的更大灾难。     

新型厌氧生物技术的研发现状与前景

伴随人类社会的进步和繁荣,环境污染、能源紧张和资源短缺问题迎面而来。由于在净化水体的同时还可产生能量或电能,也可生产有价值的化学品,厌氧生物技术已成为环境工程与能源及资源工程中的一项重要技术,越来越受到人们的重视。本文分别对厌氧发酵生物制氢技术、厌氧膜生物反应器技术、微生物燃料电池技术以及厌氧生物技术生产化学品4种新型厌氧生物技术进行综述．     

以色列的农业生物技术

尽管以色列在其它学科上取得显著的成就 ,但在生物技术上的研究并不像世人所期待那样发展迅速。五年前以色列约有 50家生物技术公司 ,现在全国约有 150家 ,所研究的领域涉及到医药、诊断剂、种植业、兽医、海洋生物、ＤＮＡ技术和其它应用领域。据统计 ,1998年生物技术产业出口值为 3.5亿美元。据预测 ,到 2 0 0 0年生物技术总销售额为 5亿美元。以色列的农业生物技术现状简介如下。1　技术孵化器为了支持工业发展 ,工业贸易部首席科学家办公室正在实施一项“技术孵化器计划” ,以帮助新生企业家成功地完成其项目和商业化。许多近几年来自前…     

2007年生物产业技术研讨会筹备工作已全面展开

在生物技术产品生产中,分离纯化技术对生物技术产品的形态。收率和成本起着越来越重要的作用。在以小分子为主的传统发酵工业中,分离成本占总成本的60％左右。而在现代基因工程产品中,分离成本高达90%。因此分离纯化技术在生物技术产业化中起着十分重要的作用。为推动生物产业中应用技术的进步与发展,化学工业出版社和中国生物工程学会决定于2007年举办以工业生物技术及分离纯化技术为主题的专题研讨会。在邀请国内外知名专家作报告的同时,为科研院校（所）及企业提供交流与展示的平台。     

工业生物技术：工业可持续发展最有希望的技术——欧阳平凯院士访谈

——请您简单介绍一下目前工业生物技术发展现状与发展趋势。欧阳院士：工业生物技术是指在工业规模生产过程中运用微生物或酶为催化剂进行物质加工制造的技术．广泛应用于化工、制药、食品、饲料、轻纺、矿产、材料和能源等工业领域。工业生物技术是生物技术发展史上继医药生物技术、农业生物技术之后的第三次浪潮．对于解决人类社会目前面临的资源、能源与环境等诸多重要问题具有重要意义。     

焦磷酸测序技术在确认北京严重急性呼吸综合征(SARS)病毒株并检测基因突变中的应用

结合严重急性呼吸综合征(SARS)病毒株序列信息分析和高通量测序技术,建立一种快速、简单地确定SARS病毒株并筛查SARS病毒突变位点和突变频率的方法。从感染人SARS病毒的Vero-6细胞中提取病毒RNA,反转录为cDNA后,PCR扩增目的基因片段,采用焦磷酸测序技术(Pyrosequencing Technology,PSQ)进行第2601、7919、9479、19838多个碱基突变位点测序和突变频率分析。通过测序分析多个可能出现突变的位点,确定了该病毒为北京流行株,同时发现第7919位碱基发生了A／G突变。PSQ技术对于高通量筛选研究病毒基因的突变和确定病毒株型别有着简单、快速、灵敏的特点。利用生物信息学分析核酸多态性,结合实验验证,可以确定SARS病毒流行株的特征,有利于对突发事件及早确定传染来源。     

mRNA差异显示技术及其在园艺植物上的应用（综述）

mRNA差异显示技术是鉴别基因差异表达方法之一,已在生物技术相关领域中广泛应用.本文介绍mRNA差异显示技术的基本原理及主要优缺点,较详细地综述了该技术在园艺植物生物技术方面的最新应用状况及取得的研究结果.     

藻类生物技术与海洋产业发展

藻类生物技术与海洋产业发展周百成,曾呈奎（中国科学院海洋研究所）生物技术（Ｂｉｏｔｅｃｈｎｏｌｏｇｙ）或称生物工程是在分子生物学、细胞生物学的理论基础上建立起来的一个现代技术体系。它是生物科学与技术科学的综合性边缘学科。海洋生物学与生物技术相结合,产生了海洋生物技术（Ｍａｒｉｎｅｂｉｏｔｅｃｈｎｏｌｏｇｙ）这一新的领域。     

临床应用重组SARS病毒双抗原夹心诊断试剂盒的检测效果评价

严重急性呼吸综合征(severe acute respiralory syndrome,SARS)的临床表现为非典型性肺炎.继加拿大首次完成SARS病毒株Tor2的全基因组测序后[1],世界卫生组织(WTO)宣布一种新型的冠状病毒(coronavirus)是引发SARS的病原体[2,3].由于SARS具有极强的传染性和较高的病死率(5%～15%),且早期疾病体征较难与某些非SARS病毒引起的非典型肺炎相区分[4],由此导致大量疑似病例无法确诊,以及因误诊引起的交叉感染给人们造成巨大的心理压力和社会恐慌.所以,建立快速、准确的早期诊断方法显得尤为重要.目前的实验室诊断方法中,主要有基于病毒抗体检测的免疫荧光法和酶联免疫吸附试验(ELISA),以及基于基因检测的多聚酶链式反应(PCR)和基因芯片法.其中ELISA主要是使用病毒裂解抗原,检测病毒IgG及IgM抗体的间接ELISA.由于病毒裂解抗原的复杂性,以及间接ELISA中二抗带来的假阳性结果,间接ELISA试剂在正常人群中有1.5%～2%的阳性结果.     

SARS冠状病毒感染恒河猴的病毒、血清学检测研究

[目的]对感染SARS-CoV的恒河猴进行病毒、血清学等指标检测及研究,确定模型动物成功感染,并为SARS发病机制,疫苗评价,药物筛选确定参考指标。[方法]SARSCo-V经鼻腔接种8只恒河猴,在感染的第1天开始到5、7、10、15、20、30和60天分别安乐死时,不同时间取咽拭子、血液和脏器,进行病毒分离,RT-PCR检测和抗体测定。[结果]用巢式RT-PCR在感染后每天提取的咽拭子标本中检测SARS-CoV的RNA,以细胞培养冠状病毒为阳性对照,以正常恒河猴咽拭子为阴性对照,在8只动物病毒接种第5天开始可检测到大小为797bp的目的条带,阳性检出最长可持续到第15天。进一步用病毒分离实验对PCR结果进行确证,8只动物中的5只恒河猴接种5天的咽拭子标本中,经Vero细胞培养,细胞产生了典型细胞病变(CPE),提示SARS冠状病毒能感染恒河猴并有病毒的复制和排毒。IFA方法证实为SRAS-CoV抗原存在。SARS-CoV感染恒河猴后,可以检测出免疫反应。在SARS冠状病毒接种前和接种后第5、8、11、15、19、23、26、30、34、每隔4-7天以及安乐死时采血,制备血清测定抗体,8只恒河猴接种病毒前均血清中SARS冠状病毒特异性抗体IgG为阴性,10天后安乐处死的5只感染猴在11-15天开始,至安乐死时,均为阳性。IgG阳性的5只恒河猴均有一定的中和抗体产生,且对SARS病毒感染细胞有一定的保护性。感染SARS病毒猴后与正常猴比较,其细胞杀伤效应明显增强。感染SARS-CoV的恒河猴不仅出现与SARS患者类似的临床和病理学改变,也在一定时期内排毒,出现特异免疫反应,这些指标均可作为药物筛选、疫苗评价等方面的重要参数。     

SARS病毒感染动物模型

SARS-CoV感染动物模型的建立可加深对SARS病原学的了解和发病机制的研究,加速实验室诊断技术的建立、抗病毒药物的筛选和疫苗的开发,同时也有助于给该病一个更精确的定义。可以说SARS动物模型的建立,不但是SARS研究的瓶颈问题,其应用更是贯穿SARS研究的整个过程。到目前为止,已经报道有4种非人灵长类动物(恒河猴、食蟹猴、绒猴、非洲绿猴)和6种啮齿类动物(大鼠、小鼠、豚鼠、田鼠、仓鼠、转基因鼠),以及雪貂、家猫等可以作为SARS动物模型用于实验研究,并已经开始利用动物模型进行疫苗和药物的安全性和有效性评价。本文就已报道的各类SARS动物模型进行综述,并根据动物模型和SARS患者的比对,提出动物模型建立的技术要点。     

Evolution of genomes, host shifts and the geographic spread of SARS-CoV and related coronaviruses

Severe acute respiratory syndrome (SARS) is a novel human illness caused by a previously unrecognized coronavirus (CoV) termed SARS‐CoV. There are conflicting reports on the animal reservoir of SARS‐CoV. Many of the groups that argue carnivores are the original reservoir of SARS‐CoV use a phylogeny to support their argument. However, the phylogenies in these studies often lack outgroup and rooting criteria necessary to determine the origins of SARS‐CoV. Recently, SARS‐CoV has been isolated from various species of Chiroptera from China (e.g., Rhinolophus sinicus) thus leading to reconsideration of the original reservoir of SARS‐CoV. We evaluated the hypothesis that SARS‐CoV isolated from Chiroptera are the original zoonotic source for SARS‐CoV by sampling SARS‐CoV and non‐SARS‐CoV from diverse hosts including Chiroptera, as well as carnivores, artiodactyls, rodents, birds and humans. Regardless of alignment parameters, optimality criteria, or isolate sampling, the resulting phylogenies clearly show that the SARS‐CoV was transmitted to small carnivores well after the epidemic of SARS in humans that began in late 2002. The SARS‐CoV isolates from small carnivores in Shenzhen markets form a terminal clade that emerged recently from within the radiation of human SARS‐CoV. There is evidence of subsequent exchange of SARS‐CoV between humans and carnivores. In addition SARS‐CoV was transmitted independently from humans to farmed pigs (Sus scrofa). The position of SARS‐CoV isolates from Chiroptera are basal to the SARS‐CoV clade isolated from humans and carnivores. Although sequence data indicate that Chiroptera are a good candidate for the original reservoir of SARS‐CoV, the structural biology of the spike protein of SARS‐CoV isolated from Chiroptera suggests that these viruses are not able to interact with the human variant of the receptor of SARS‐CoV, angiotensin‐converting enzyme 2 (ACE2). In SARS‐CoV we study, both visually and statistically, labile genomic fragments and, putative key mutations of the spike protein that may be associated with host shifts. We display host shifts and candidate mutations on trees projected in virtual globes depicting the spread of SARS‐CoV. These results suggest that more sampling of coronaviruses from diverse hosts, especially Chiroptera, carnivores and primates, will be required to understand the genomic and biochemical evolution of coronaviruses, including SARS‐CoV. © The Willi Hennig Society 2008.     

Orchitis: a complication of severe acute respiratory syndrome (SARS)

Severe acute respiratory syndrome (SARS) coronavirus has been known to damage multiple organs; however, little is known about its impact on the reproductive system. In the present study, we analyzed the pathological changes of testes from six patients who died of SARS. Results suggested that SARS caused orchitis. All SARS testes displayed widespread germ cell destruction, few or no spermatozoon in the seminiferous tubule, thickened basement membrane, and leukocyte infiltration. The numbers of CD3+ T lymphocytes and CD68+ macrophages increased significantly in the interstitial tissue compared with the control group (P < 0.05). SARS viral genomic sequences were not detected in the testes by in situ hybridization. Immunohistochemistry demonstrated abundant IgG precipitation in the seminiferous epithelium of SARS testes, indicating possible immune response as the cause for the damage. Our findings indicated that orchitis is a complication of SARS. It further suggests that the reproductive functions should be followed and evaluated in recovered male SARS patients.     

Understanding SARS with Wolfram approach

Stepping acquired immunodeficiency syndrome (AIDS), severe acute respiratory syndrome (SARS) as another type of disease has been threatening mankind since late last year. Many scientists worldwide are making great efforts to study the etiology of this disease with different approaches. 13 species of SARS virus have been sequenced. However, most people still largely rely on the traditional methods with some disadvantages. In this work, we used Wolfram approach to study the relationship among SARS viruses and between SARS viruses and other types of viruses, the effect of variations on the whole genome and the advantages in the analysis of SARS based on this novel approach. As a result, the similarities between SARS viruses and other coronavirusxes are not really higher than those between SARS viruses and non-coronaviruses.     

血中检测SARS冠状病毒N蛋白在SARS实验室早期诊断中的作用

为明确严重急性呼吸综合症(SARS)冠状病毒N蛋白在SARS实验室早期诊断中的作用,通过微量中和试验及酶联免疫方法、间接免疫荧光法检测疑似病人恢复期血清(大于28天)中SARS-IgG抗体,确诊SARS患者。同时收集发病不同时期SARS及普通发热病人血清,利用酶联免疫方法检测SARS-CoVN蛋白,并与荧光定量PCR早期诊断方法相比较。共检测：广州地区2003年12月～2004．年1月新发4例确诊SARS患者不同时期的血液和咽漱液标本;恢复期血清SARS-CoV中和抗体阳性病人不同时期的血清46份;广州地区2003年1月～4月临床确诊SARS患者159例的血清和56例疑似患者血清;非SARS普通发热病人血清97份;正常人体检血清100份。结果：4例新发SARS患者的不同时期标本中,3例患者急性期血均检出N蛋白,优于常用的荧光定量PCR检测方法。46份SARS-CoV中和抗体阳性的血清标本,N蛋白检出率为100％。159例临床确诊病例中,发病早期5天以内SARS-CoVN蛋白的检出率为92．3％,随后呈现逐步下降的趋势,在发病第18天仍可检出。56例临床疑似患者发病早期也有23．2％检出率。而97例普通发热病人及100份正常人血清中均未能检测出SARS-CoVN蛋白。表明在血清中检测SARS冠状病毒N蛋白的方法敏感性和特异性都好,对SARS实验室早期诊断具有重要作用。     

The putative protein 6 of the severe acute respiratory syndrome-associated coronavirus: expression and functional characterization

The SARS-CoV open reading frame 6 (ORF6) is transcribed into mRNA6 and encodes a putative 7.5 kDa accessory protein, SARS 6, with unknown function. In this study, we have confirmed the SARS 6 protein expression in lung and intestine tissues of the SARS patients and in SARS-CoV infected Vero E6 cells by immunohistochemistry. Further studies by immunoblot and confocal microscopy analyses revealed the expression and the endoplasmic reticulum (ER) localization of the recombinant SARS 6 protein in mammalian cells. Expression of SARS 6 protein in mammalian cells elicits biological activity of stimulating cellular DNA synthesis.     

Comparing the binding properties of peptides mimicking the Envelope protein of SARS‐CoV and SARS‐CoV‐2 to the PDZ domain of the tight junction‐associated PALS1 protein

The Envelope protein (E) is one of the four structural proteins encoded by the genome of SARS‐CoV and SARS‐CoV‐2 Coronaviruses. It is an integral membrane protein, highly expressed in the host cell, which is known to have an important role in Coronaviruses maturation, assembly and virulence. The E protein presents a PDZ‐binding motif at its C‐terminus. One of the key interactors of the E protein in the intracellular environment is the PDZ containing protein PALS1. This interaction is known to play a key role in the SARS‐CoV pathology and suspected to affect the integrity of the lung epithelia. In this paper we measured and compared the affinity of peptides mimicking the E protein from SARS‐CoV and SARS‐CoV‐2 for the PDZ domain of PALS1, through equilibrium and kinetic binding experiments. Our results support the hypothesis that the increased virulence of SARS‐CoV‐2 compared to SARS‐CoV may rely on the increased affinity of its Envelope protein for PALS1.     

SARS--beginning to understand a new virus

The 114-day epidemic of the severe acute respiratory syndrome (SARS) swept 29 countries, affected a reported 8,098 people, left 774 patients dead and almost paralyzed the Asian economy. Aggressive quarantine measures, possibly aided by rising summer temperatures, successfully terminated the first eruption of SARS and provided at least a temporal break, which allows us to consolidate what we have learned so far and plan for the future. Here, we review the genomics of the SARS coronavirus (SARS-CoV), its phylogeny, antigenic structure, immune response and potential therapeutic interventions should the SARS epidemic flare up again.