首页 > 最新文献

Biotechnology and Genetic Engineering Reviews最新文献

英文 中文
Use and Applications of Subtractive Antibody Screening 减法抗体筛选的使用和应用
Pub Date : 2000-08-01 DOI: 10.1080/02648725.2000.10648000
P. Bickel, H. Lodish, Philipp E. Scherer
Information about where and when genes are expressed is critical to understanding the function of the proteins that they encode in both health and disease. This concept is driving robust technology development in the field of functional genomics. Gene chips and other gene array systems permit the expression of thousands of genes to be surveyed simultaneously. A limitation of these approaches is that differential expression is detected at the level of RNA. Due to regulatory mechanisms that operate at the translational and post-translational levels, the absolute amounts of mRNA expression of a particular gene may not reflect the levels of its protein. Nevertheless, it is the level of protein that is ultimately more informative biologically in most cases. Another limitation is that gene expression data do not reveal important functional details, such as secondary modifications of proteins or their subcellular localization. The emerging field of proteomics addresses these limitations by working at the protein level to identify differential expression. By this approach, proteins in complex mixtures, such as cell lysates, are separated from one another chromatographically or electrophoretically, and then identified by such methods as microsequencing or mass spectroscopy, both of which are costly and labour intensive. We developed subtractive antibody screening (SAS) (Scherer etal., 1998) as a tool for functional proteomics (Figure 15.1). Our goal was to create a method by which particular subsets of differentially expressed proteins could be identified and their corresponding cDNAs cloned systematically. Further, we required that the method not depend on high cost equipment or services. In short, SAS relies on the generation
关于基因何时何地表达的信息对于理解它们在健康和疾病中编码的蛋白质的功能至关重要。这一概念正在推动功能基因组学领域的强劲技术发展。基因芯片和其他基因阵列系统允许同时调查数千个基因的表达。这些方法的局限性是在RNA水平上检测差异表达。由于在翻译和翻译后水平上起作用的调控机制,特定基因mRNA的绝对表达量可能不能反映其蛋白质水平。然而,在大多数情况下,蛋白质的水平最终提供了更多的生物学信息。另一个限制是基因表达数据不能揭示重要的功能细节,如蛋白质的二次修饰或它们的亚细胞定位。新兴的蛋白质组学领域通过在蛋白质水平上识别差异表达来解决这些限制。通过这种方法,复杂混合物中的蛋白质,如细胞裂解物,通过色谱或电泳相互分离,然后通过微测序或质谱等方法进行鉴定,这两种方法都是昂贵且劳动密集型的。我们开发了减法抗体筛选(SAS) (Scherer等)。作为功能蛋白质组学的工具(图15.1)。我们的目标是创造一种方法,通过这种方法可以识别差异表达蛋白的特定亚群,并系统地克隆它们相应的cdna。此外,我们要求该方法不依赖于高成本的设备或服务。简而言之,SAS依赖于代
{"title":"Use and Applications of Subtractive Antibody Screening","authors":"P. Bickel, H. Lodish, Philipp E. Scherer","doi":"10.1080/02648725.2000.10648000","DOIUrl":"https://doi.org/10.1080/02648725.2000.10648000","url":null,"abstract":"Information about where and when genes are expressed is critical to understanding the function of the proteins that they encode in both health and disease. This concept is driving robust technology development in the field of functional genomics. Gene chips and other gene array systems permit the expression of thousands of genes to be surveyed simultaneously. A limitation of these approaches is that differential expression is detected at the level of RNA. Due to regulatory mechanisms that operate at the translational and post-translational levels, the absolute amounts of mRNA expression of a particular gene may not reflect the levels of its protein. Nevertheless, it is the level of protein that is ultimately more informative biologically in most cases. Another limitation is that gene expression data do not reveal important functional details, such as secondary modifications of proteins or their subcellular localization. The emerging field of proteomics addresses these limitations by working at the protein level to identify differential expression. By this approach, proteins in complex mixtures, such as cell lysates, are separated from one another chromatographically or electrophoretically, and then identified by such methods as microsequencing or mass spectroscopy, both of which are costly and labour intensive. We developed subtractive antibody screening (SAS) (Scherer etal., 1998) as a tool for functional proteomics (Figure 15.1). Our goal was to create a method by which particular subsets of differentially expressed proteins could be identified and their corresponding cDNAs cloned systematically. Further, we required that the method not depend on high cost equipment or services. In short, SAS relies on the generation","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"164 1","pages":"417 - 432"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83590119","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 3
The Effects of Physical Forces on Cartilage Tissue Engineering 物理力对软骨组织工程的影响
Pub Date : 2000-08-01 DOI: 10.1080/02648725.2000.10648004
C. Heath
Despite long-held beliefs to the contrary, articularcartilage, which provides articulating joints with a nearly frictionless, weight-distributing surface for transferring forces between bones, does have a limited ability for self..repair (Cheung et al., 1978; Mankin, 1982; Grande et at., 1989). With age, repeated overuse, or injury, however, natural mechanislns may be inadequate for repairing the damage. Mechanical breakdown of the articulating surfaces within freely moving (diarthrodial or synovial) joints results in osteoarthritis, which afflicts over 30 million people in the U.S. alone (Mow et al., 1992). Current treatment of severely damaged cartilage usually involves total replacement of affected joints with artificial prostheses or transplantation of donor tissue, each of which has its limitations. Artificial prostheses, because of their limited lifetime and need for replacement, are not the best option for younger patients. Donor tissue, on the other hand, is not always available, especially in the size and shape needed. Promising new therapies already in clinical use or still under study include the development of replacement cartilage ill vivo, either by injecting cells into the tissue (Brittberg et ai., 1994) or by implanting a matrix that was seeded with cells ill vitro (Frenkel et aI., 1997). Another alternative is implantation of tissue constructs that have already been partially developed in vitro. A nunlber of studies have shown that cartilage-like tissue can be regenerated in vitro, and that development of the tissue matrix is enhanced in culture systenlS simulating aspects of the native environment, ie that provide a compatible three-dimensional support. structure, good mass trdnsfer, and a physical (and/or chemical) stimulus. While progress has been made in growing tissue that has bioclzel1zical and even histological similarity, in most cases the
尽管长期以来人们持有相反的观点,关节软骨为关节提供了几乎无摩擦的重量分布表面,用于在骨骼之间传递力,但它确实具有有限的自我修复能力(Cheung等人,1978;Mankin, 1982;格兰德。, 1989)。然而,随着年龄的增长,反复过度使用或受伤,自然机制可能不足以修复损伤。在自由活动的关节(腹泻关节或滑膜关节)内关节表面的机械破坏导致骨关节炎,仅在美国就有超过3000万人患有骨关节炎(Mow et al., 1992)。目前对严重受损软骨的治疗通常包括用人工假体或供体组织移植完全替代受影响的关节,每种方法都有其局限性。由于人工假体的使用寿命有限,需要更换,所以对年轻患者来说不是最好的选择。另一方面,供体组织并不总是可用的,尤其是在所需的大小和形状上。有希望的新疗法已经在临床使用或仍在研究中,包括通过向组织中注射细胞来发展体内软骨替代物(Brittberg等)。(frankel et aI.), 1994)或通过植入一种基质,该基质用离体细胞播种(Frenkel et aI.)。, 1997)。另一种选择是植入已经在体外部分发育的组织结构。许多研究表明,软骨样组织可以在体外再生,并且在模拟自然环境的培养系统中,组织基质的发育得到加强,即提供兼容的三维支持。结构,良好的传质,和物理(和/或化学)刺激。虽然在培养具有生物类型学甚至组织学相似性的组织方面已经取得了进展,但在大多数情况下,生物类型学和生物学的相似性是不可避免的
{"title":"The Effects of Physical Forces on Cartilage Tissue Engineering","authors":"C. Heath","doi":"10.1080/02648725.2000.10648004","DOIUrl":"https://doi.org/10.1080/02648725.2000.10648004","url":null,"abstract":"Despite long-held beliefs to the contrary, articularcartilage, which provides articulating joints with a nearly frictionless, weight-distributing surface for transferring forces between bones, does have a limited ability for self..repair (Cheung et al., 1978; Mankin, 1982; Grande et at., 1989). With age, repeated overuse, or injury, however, natural mechanislns may be inadequate for repairing the damage. Mechanical breakdown of the articulating surfaces within freely moving (diarthrodial or synovial) joints results in osteoarthritis, which afflicts over 30 million people in the U.S. alone (Mow et al., 1992). Current treatment of severely damaged cartilage usually involves total replacement of affected joints with artificial prostheses or transplantation of donor tissue, each of which has its limitations. Artificial prostheses, because of their limited lifetime and need for replacement, are not the best option for younger patients. Donor tissue, on the other hand, is not always available, especially in the size and shape needed. Promising new therapies already in clinical use or still under study include the development of replacement cartilage ill vivo, either by injecting cells into the tissue (Brittberg et ai., 1994) or by implanting a matrix that was seeded with cells ill vitro (Frenkel et aI., 1997). Another alternative is implantation of tissue constructs that have already been partially developed in vitro. A nunlber of studies have shown that cartilage-like tissue can be regenerated in vitro, and that development of the tissue matrix is enhanced in culture systenlS simulating aspects of the native environment, ie that provide a compatible three-dimensional support. structure, good mass trdnsfer, and a physical (and/or chemical) stimulus. While progress has been made in growing tissue that has bioclzel1zical and even histological similarity, in most cases the","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"67 1","pages":"533 - 552"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"81105648","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 14
The Use of Chromatography to Manufacture Purer and Safer Plasma Products 用色谱法生产更纯净、更安全的血浆产品
Pub Date : 2000-08-01 DOI: 10.1080/02648725.2000.10647987
A. Johnston, Wayne Adcock
Chromatography is as old as the bible. According to the Old Testament, Moses realized that the rotten cellulose of the tree could be used to exchange the magnesium ions in the water, leaving the water sweet to taste. Centuries later, we now have a better understanding of how chromatography can be harnessed to purify not just water but one of the most precious of juices, blood. Blood transfusion medicine can be traced back to classical Greek times when it was based on Hippocratic and Galenic concepts of four humours — sanguine, phlegmatic, melancholic and bilious. Donation from the milder species of gentle disposition was supposed to have a calming influence on the recipient of the blood. Centuries later, we have a better understanding of what makes blood so special and how to transfuse it and its derivatives to a patient in a way that is efficacious and safe. This review looks at how chromatography came to play a key role in purifying important therapeutic products from the blood. The threat of emerging blood-borne
色谱法和圣经一样古老。根据《旧约》,摩西意识到树的腐烂纤维素可以用来交换水中的镁离子,使水尝起来很甜。几个世纪后,我们现在对如何利用色谱法不仅净化水,而且净化最珍贵的汁液之一——血液有了更好的了解。输血医学可以追溯到古典希腊时代,当时它是基于希波克拉底和盖伦的四种幽默的概念-多血,粘液,忧郁和胆汁。来自性情温和的温和物种的捐赠被认为对接受血液的人有镇静作用。几个世纪后,我们对血液的特殊之处有了更好的了解,也更了解如何以有效和安全的方式将血液及其衍生物输往病人体内。这篇综述着眼于色谱是如何在从血液中纯化重要治疗产品中发挥关键作用的。新出现的血源性威胁
{"title":"The Use of Chromatography to Manufacture Purer and Safer Plasma Products","authors":"A. Johnston, Wayne Adcock","doi":"10.1080/02648725.2000.10647987","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647987","url":null,"abstract":"Chromatography is as old as the bible. According to the Old Testament, Moses realized that the rotten cellulose of the tree could be used to exchange the magnesium ions in the water, leaving the water sweet to taste. Centuries later, we now have a better understanding of how chromatography can be harnessed to purify not just water but one of the most precious of juices, blood. Blood transfusion medicine can be traced back to classical Greek times when it was based on Hippocratic and Galenic concepts of four humours — sanguine, phlegmatic, melancholic and bilious. Donation from the milder species of gentle disposition was supposed to have a calming influence on the recipient of the blood. Centuries later, we have a better understanding of what makes blood so special and how to transfuse it and its derivatives to a patient in a way that is efficacious and safe. This review looks at how chromatography came to play a key role in purifying important therapeutic products from the blood. The threat of emerging blood-borne","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"70 1","pages":"37 - 70"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84129097","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 23
Genetic Susceptibility in Infectious Diseases 传染病的遗传易感性
Pub Date : 2000-08-01 DOI: 10.1080/02648725.2000.10647994
M. Thursz
The outcome of infectious disease varies tremendously between individuals due to a number of factors and may therefore be viewed by the geneticist as complex traits. The identification of genes which influence disease outcome is, at present, a resource-intensive project and therefore should not be undertaken without clear evidence, preferably from twin studies, that the genetic contribution is significant. Although three principal techniques are available for the identification of disease susceptibility alleles, they are not applicable to all infectious diseases for logistical reasons. Whether a candidate polymorphic gene is identified through allele sharing studies, from interspecific crosses or taken from the currently available candidate list, the final evaluation will require carefully conducted disease association studies. As we move into the post genomic era, the identification of candidate polymorphisms and the characterization of their functional significance will rapidly increase, which will make the analysis of disease susceptibility in infectious diseases steadily more tractable.
由于许多因素,传染病的结果在个体之间差异很大,因此可能被遗传学家视为复杂的特征。目前,确定影响疾病结果的基因是一项资源密集的项目,因此,在没有明确证据(最好是来自双胞胎研究的证据)表明基因的贡献是显著的情况下,不应进行这项工作。虽然有三种主要技术可用于确定疾病易感性等位基因,但由于后勤原因,它们并不适用于所有传染病。无论候选多态性基因是通过等位基因共享研究、种间杂交还是从目前可用的候选基因列表中确定的,最终的评估都需要仔细进行疾病关联研究。随着我们进入后基因组时代,候选多态性的鉴定及其功能意义的表征将迅速增加,这将使传染病的疾病易感性分析变得更加容易。
{"title":"Genetic Susceptibility in Infectious Diseases","authors":"M. Thursz","doi":"10.1080/02648725.2000.10647994","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647994","url":null,"abstract":"The outcome of infectious disease varies tremendously between individuals due to a number of factors and may therefore be viewed by the geneticist as complex traits. The identification of genes which influence disease outcome is, at present, a resource-intensive project and therefore should not be undertaken without clear evidence, preferably from twin studies, that the genetic contribution is significant. Although three principal techniques are available for the identification of disease susceptibility alleles, they are not applicable to all infectious diseases for logistical reasons. Whether a candidate polymorphic gene is identified through allele sharing studies, from interspecific crosses or taken from the currently available candidate list, the final evaluation will require carefully conducted disease association studies. As we move into the post genomic era, the identification of candidate polymorphisms and the characterization of their functional significance will rapidly increase, which will make the analysis of disease susceptibility in infectious diseases steadily more tractable.","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"38 1","pages":"255 - 266"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85370305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 9
Possible Molecular Mechanisms Involved in Nickel, Zinc and Selenium Hyperaccumulation in Plants 植物镍、锌、硒超积累的可能分子机制
Pub Date : 2000-08-01 DOI: 10.1080/02648725.2000.10647999
M. Persans, D. Salt
Most hyperaccumulator species are able to accumulate between 1-5% of their biomass as metal. However, these plants are often small, slow growing, and do not produce a high biomass. Phytoextraction, a cost-effective, in situ, plant-based approach to soil remediation takes advantage of the remarkable ability of hyperaccumulating plants to concentrate metals from the soil and accumulate them in their harvestable, above-ground tissues (Salt et ai., 1998). However, to make use of the valuable genetic resources identified in metal hyperaccumulating species, it win be necessary to transfer this material to high biomass, rapidly growing crop plants (Salt et al., 1998). These plants would then be ideally suited to the phytoremediation process, having the ability to produce a large amount of metal-rich plant biomass for rapid harvest and soil cleanup. It is becoming clear that the hyperaccumu]ator plant's genetic material could also be very valuable in enhancing the nutritional value of human foodstuffs. Malnutrition remains one of the most serious problems facing mankind and1 although remarkable improvements in crop productivity have been made over the last twenty years, it is now clear that this has been made at the expense of the nutritional value of the foodstuff produced. Deficiencies in such micronutrients as iron, zinc~ selenium, iodine and vitamin A are often referred to as the 'hidden hunger'. Substantial efforts
大多数超积累物种能够以金属形式积累其生物量的1-5%。然而,这些植物通常很小,生长缓慢,不能产生高生物量。植物提取是一种具有成本效益的、原位的、以植物为基础的土壤修复方法,它利用了超积累植物从土壤中浓缩金属并将其积累在其可收获的地上组织中的非凡能力(Salt等)。, 1998)。然而,为了利用在金属超积累物种中发现的宝贵遗传资源,有必要将这种物质转移到高生物量、快速生长的作物植物中(Salt等,1998年)。这些植物将非常适合植物修复过程,有能力产生大量富含金属的植物生物量,用于快速收获和土壤清理。越来越清楚的是,超蓄积物植物的遗传物质在提高人类食品的营养价值方面也非常有价值。营养不良仍然是人类面临的最严重的问题之一。尽管近二十年来作物产量有了显著的提高,但现在很清楚,这是以牺牲所生产的粮食的营养价值为代价的。缺乏铁、锌、硒、碘和维生素A等微量营养素通常被称为“隐性饥饿”。大量的努力
{"title":"Possible Molecular Mechanisms Involved in Nickel, Zinc and Selenium Hyperaccumulation in Plants","authors":"M. Persans, D. Salt","doi":"10.1080/02648725.2000.10647999","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647999","url":null,"abstract":"Most hyperaccumulator species are able to accumulate between 1-5% of their biomass as metal. However, these plants are often small, slow growing, and do not produce a high biomass. Phytoextraction, a cost-effective, in situ, plant-based approach to soil remediation takes advantage of the remarkable ability of hyperaccumulating plants to concentrate metals from the soil and accumulate them in their harvestable, above-ground tissues (Salt et ai., 1998). However, to make use of the valuable genetic resources identified in metal hyperaccumulating species, it win be necessary to transfer this material to high biomass, rapidly growing crop plants (Salt et al., 1998). These plants would then be ideally suited to the phytoremediation process, having the ability to produce a large amount of metal-rich plant biomass for rapid harvest and soil cleanup. It is becoming clear that the hyperaccumu]ator plant's genetic material could also be very valuable in enhancing the nutritional value of human foodstuffs. Malnutrition remains one of the most serious problems facing mankind and1 although remarkable improvements in crop productivity have been made over the last twenty years, it is now clear that this has been made at the expense of the nutritional value of the foodstuff produced. Deficiencies in such micronutrients as iron, zinc~ selenium, iodine and vitamin A are often referred to as the 'hidden hunger'. Substantial efforts","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"26 1","pages":"389 - 416"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83071326","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 43
Gene Therapy: Development of Immunostimulatory Treatments for Cancer 基因治疗:癌症免疫刺激治疗的发展
Pub Date : 2000-08-01 DOI: 10.1080/02648725.2000.10648003
M. Gilligan, P. Knox, P. Searle
Gene therapy encompasses a broad range of strategies, which aim to treat human diseases by the transfer of genetic infornlation. The idea was initially conceived for the treatment of inherited, monogenic disorders such as cystic fibrosis, in which the disease phenotype is due to the lack of a properly functional gene product in certain tissues. In principle, transfer of a functional gene encoding the relevant, wild-type protein could restore the affected cells to nonnality. It was soon realized that there are many other situations in which the introduction of specific genetic modifications to target cells could confer properties which could be of benefit in Jnany other clinical situations, including cardiovascular~neurological and infectious diseases, and cancer. There are numerous approaches to cancer gene therapy; the nlajority are designed to treat patients who have presented with cancer, rather than focusing on pre-emptive treatnlent of patients with known inherited predisposition to cancer. Approaches include interference with oncogene action within tumour cells; restoration of tumoursuppressor gene function; and expression of enzymes that enable the tumour cells to activate non-toxic prodrugs to cytotoxic species. This review focuses exclusively on cancer gene therapy strategies that are intended to induce immune responses against the malignant cells~ The approach is attractive, particularly because the disseminated nature of many cancers at later stages of the disease, and often at presentation, poses
基因治疗包括一系列广泛的策略,其目的是通过遗传信息的转移来治疗人类疾病。这个想法最初是为了治疗遗传性单基因疾病,如囊性纤维化,其中疾病的表型是由于某些组织中缺乏功能正常的基因产物。原则上,转移编码相关野生型蛋白的功能基因可以使受影响的细胞恢复正常。人们很快意识到,在许多其他情况下,将特定的遗传修饰引入目标细胞可能会赋予对许多其他临床情况有益的特性,包括心血管、神经和传染病以及癌症。癌症基因治疗有很多方法;大多数药物是为治疗已经出现癌症的患者而设计的,而不是针对已知遗传易感性的癌症患者进行先发制人的治疗。方法包括干扰肿瘤细胞内癌基因的作用;肿瘤抑制基因功能的恢复;以及酶的表达,使肿瘤细胞能够激活对细胞毒性物种无毒的前药。这篇综述专门关注癌症基因治疗策略,旨在诱导对恶性细胞的免疫反应。这种方法是有吸引力的,特别是因为许多癌症在疾病晚期的弥散性,通常在出现时,会造成疾病
{"title":"Gene Therapy: Development of Immunostimulatory Treatments for Cancer","authors":"M. Gilligan, P. Knox, P. Searle","doi":"10.1080/02648725.2000.10648003","DOIUrl":"https://doi.org/10.1080/02648725.2000.10648003","url":null,"abstract":"Gene therapy encompasses a broad range of strategies, which aim to treat human diseases by the transfer of genetic infornlation. The idea was initially conceived for the treatment of inherited, monogenic disorders such as cystic fibrosis, in which the disease phenotype is due to the lack of a properly functional gene product in certain tissues. In principle, transfer of a functional gene encoding the relevant, wild-type protein could restore the affected cells to nonnality. It was soon realized that there are many other situations in which the introduction of specific genetic modifications to target cells could confer properties which could be of benefit in Jnany other clinical situations, including cardiovascular~neurological and infectious diseases, and cancer. There are numerous approaches to cancer gene therapy; the nlajority are designed to treat patients who have presented with cancer, rather than focusing on pre-emptive treatnlent of patients with known inherited predisposition to cancer. Approaches include interference with oncogene action within tumour cells; restoration of tumoursuppressor gene function; and expression of enzymes that enable the tumour cells to activate non-toxic prodrugs to cytotoxic species. This review focuses exclusively on cancer gene therapy strategies that are intended to induce immune responses against the malignant cells~ The approach is attractive, particularly because the disseminated nature of many cancers at later stages of the disease, and often at presentation, poses","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"11 1","pages":"497 - 532"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87971689","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 6
Deriving Meaning from Genomic Information 从基因组信息中获得意义
Pub Date : 2000-08-01 DOI: 10.1080/02648725.2000.10647989
Raymond J. Cho
As sequencing of the hUlnan genolne draws to a close, the fruits of this vision have already achieved startling 1l1aturity. By leveraging DNA sequence information toward robust~ new technological platforms, researchers are rapidly recharting the 1l1odern course of molecular genetics. Until now, the currencies of genolnic experimentation have renlained recognizable, if vastly increased in scope. We are still assaying the regulation of gene activity or linking phenotypes to genetic variation only on a scale fouT or five orders of magnitude greater than before. Indeed, many in the scientific comnlunity first elnbraced genomics for its pronlise of a vealth of data traditionally generated through more painstaking means. But large-scale technologies presage far deeper change in the very way we think about biological systeJns. The results of experilllental genoJnics noisy~ sparse in context, and overwhelmingly vast in scope resist the bounded conclusions drawn from conventional biological study. Rather, these data reflect the cOlnbinatorial con1plexity of cellular systems and challenge us to discenl the pattenls underlying biological design. GenoJllic approaches reveal not only discrete links that connect individual proteins and phenotypes, but also broad comnlunications between parts of pathways, chromosolnes, and cellular process. Ultimately, these studies may prove Inost valuable for providing answers to those questions we never set out to ask. Divining these new sorts of conclusions is a task to which biologists find themselves largely unaccuston1ed. And so, as genolnic data proliferates, accessing and drawing Ineaningful insights will soon pose as great a technological challenge as production of the data itself. In the past t'O years, nlore infornlation regarding genetic diversity and nlRNA expression has been released into the public domain than frolll the preceding ten. That this drastic acceleration can be explained primarily by largesc,l1e DNA sequencing capability and the increasing popularity of DNA an-ays
随着hUlnan基因测序接近尾声,这一愿景的成果已经取得了惊人的成熟。通过利用DNA序列信息构建强大的新技术平台,研究人员正在迅速改写分子遗传学的现代历程。直到现在,基因实验的货币仍然是可识别的,如果范围大大扩大。我们仍在分析基因活动的调控,或将表型与遗传变异联系起来,但规模比以前大了4到5个数量级。事实上,科学界的许多人最初接受基因组学,是因为它有望获得传统上通过更艰苦的手段生成的大量数据。但大规模技术预示着我们对生物系统的思考方式将发生更深层次的变化。实验基因学的结果在背景上是嘈杂的,稀疏的,而且在范围上是压倒性的,这与传统生物学研究得出的有限结论相抵触。相反,这些数据反映了细胞系统的综合复杂性,并挑战我们辨别生物设计背后的模式。基因分析方法不仅揭示了连接单个蛋白质和表型的离散联系,而且还揭示了部分通路、染色体和细胞过程之间的广泛联系。最终,这些研究可能会证明,为那些我们从未想过要问的问题提供答案是有价值的。对这些新的结论进行推测,生物学家发现自己在很大程度上还不习惯。因此,随着基因数据的激增,获取和绘制有意义的见解将很快构成与数据生产本身一样巨大的技术挑战。在过去的60年中,有关遗传多样性和nlRNA表达的更多信息被发布到公共领域,而不是之前的10年。这种急剧的加速可以主要解释为大量的,先进的DNA测序能力和DNA测序的日益普及
{"title":"Deriving Meaning from Genomic Information","authors":"Raymond J. Cho","doi":"10.1080/02648725.2000.10647989","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647989","url":null,"abstract":"As sequencing of the hUlnan genolne draws to a close, the fruits of this vision have already achieved startling 1l1aturity. By leveraging DNA sequence information toward robust~ new technological platforms, researchers are rapidly recharting the 1l1odern course of molecular genetics. Until now, the currencies of genolnic experimentation have renlained recognizable, if vastly increased in scope. We are still assaying the regulation of gene activity or linking phenotypes to genetic variation only on a scale fouT or five orders of magnitude greater than before. Indeed, many in the scientific comnlunity first elnbraced genomics for its pronlise of a vealth of data traditionally generated through more painstaking means. But large-scale technologies presage far deeper change in the very way we think about biological systeJns. The results of experilllental genoJnics noisy~ sparse in context, and overwhelmingly vast in scope resist the bounded conclusions drawn from conventional biological study. Rather, these data reflect the cOlnbinatorial con1plexity of cellular systems and challenge us to discenl the pattenls underlying biological design. GenoJllic approaches reveal not only discrete links that connect individual proteins and phenotypes, but also broad comnlunications between parts of pathways, chromosolnes, and cellular process. Ultimately, these studies may prove Inost valuable for providing answers to those questions we never set out to ask. Divining these new sorts of conclusions is a task to which biologists find themselves largely unaccuston1ed. And so, as genolnic data proliferates, accessing and drawing Ineaningful insights will soon pose as great a technological challenge as production of the data itself. In the past t'O years, nlore infornlation regarding genetic diversity and nlRNA expression has been released into the public domain than frolll the preceding ten. That this drastic acceleration can be explained primarily by largesc,l1e DNA sequencing capability and the increasing popularity of DNA an-ays","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"49 1","pages":"108 - 91"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"73811745","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
The Effect of Aeration upon the Secondary Metabolism of Microorganisms 曝气对微生物次生代谢的影响
Pub Date : 2000-08-01 DOI: 10.1080/02648725.2000.10647996
S. I. Barberel, J. R. Walker
The authors’ interest in this topic stemmed from earlier observations in these laboratories that the metabolic behaviour of fungi grown in liquid culture was very different, depending on whether they grew, without shaking, as mycelial mats or whether they grew as pellets in shake cultures (Woodhead and Walker, 1975). Culture conditions affected both the yield of secondary metabolites and extracellular enzymes. This review examines more recent work on these topics.
作者对这一主题的兴趣源于早期在这些实验室的观察,即在液体培养中生长的真菌的代谢行为非常不同,这取决于它们是在不摇晃的情况下生长成菌丝垫还是在摇晃培养中生长成球(Woodhead and Walker, 1975)。培养条件对次生代谢物和胞外酶的产量均有影响。这篇综述考察了最近在这些主题上的工作。
{"title":"The Effect of Aeration upon the Secondary Metabolism of Microorganisms","authors":"S. I. Barberel, J. R. Walker","doi":"10.1080/02648725.2000.10647996","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647996","url":null,"abstract":"The authors’ interest in this topic stemmed from earlier observations in these laboratories that the metabolic behaviour of fungi grown in liquid culture was very different, depending on whether they grew, without shaking, as mycelial mats or whether they grew as pellets in shake cultures (Woodhead and Walker, 1975). Culture conditions affected both the yield of secondary metabolites and extracellular enzymes. This review examines more recent work on these topics.","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"24 1","pages":"281 - 326"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87218855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 19
High-Density Arrays and Insights into Genome function 高密度阵列和基因组功能的洞察
Pub Date : 2000-08-01 DOI: 10.1080/02648725.2000.10647990
L. Steinmetz, Ronald W. Davis
Genome projects are producing sequence data at a very fast pace (http:// www.ncbi.nlni.nih.govlEntrez/Genomeforghtml). The discovery of the complete human genome sequence is only a few years away and a working draft with 90% coverage is promised to appear by the time of this publication (Strategy meeting on human genome sequencing, Cold Spring Harbor, 1999). In addition to the detailed sequence, biologists will receive a list of all 50-100,000 genes in the human genome and the challenge then turns towards organizing the genes and understanding how genes operate and interact to produce a living system. Traditional gene-by-gene analyses are inefficient for obtaining information about the function, regulation, and sequence variation of the thousands of genes in a genome. Highly parallel analyses are needed to be able to survey biology from a global perspective. One type of tool for studying biology from a global perspective is the high-density array, also known as a microarray, which consists of a miniaturized, high-density array of probes bound to a solid surface. Current applications have been based on DNA probes, although in theory other molecules such as proteins or small molecular weight compounds can also be arrayed at high density. Exploiting the specificity of hybridization, DNA probes on high-density arrays can detect the presence of individual target sequences in complex mixtures. This ability allows for massively parallel hybridization assays for large numbers of genes and sequences, and has been primarily applied to survey genomes for variations in mRNA expression levels or between DNA sequences. Using. high-density DNA arrays for mRNA expression studies, rapid, accurate, and
基因组计划正在以非常快的速度产生序列数据(http:// www.ncbi.nlni.nih.govlEntrez/Genomeforghtml)。人类完整基因组序列的发现只需要几年的时间,并且在本文发表时承诺出现覆盖率为90%的工作草案(人类基因组测序战略会议,冷泉港,1999)。除了详细的序列外,生物学家还将收到人类基因组中所有50-10万个基因的列表,然后挑战转向组织基因,并了解基因如何运作和相互作用以产生一个生命系统。传统的逐基因分析对于获得基因组中数千个基因的功能、调控和序列变化的信息是低效的。高度平行的分析需要能够从全球的角度来调查生物学。从全局角度研究生物学的一种工具是高密度阵列,也被称为微阵列,它由一个小型化的高密度探针阵列结合在固体表面上。目前的应用是基于DNA探针,尽管理论上其他分子如蛋白质或小分子量化合物也可以高密度排列。利用杂交的特异性,高密度阵列DNA探针可以检测复杂混合物中单个目标序列的存在。这种能力允许对大量基因和序列进行大规模平行杂交分析,并主要应用于调查基因组中mRNA表达水平或DNA序列之间的差异。使用。用于mRNA表达研究的高密度DNA阵列,快速,准确,和
{"title":"High-Density Arrays and Insights into Genome function","authors":"L. Steinmetz, Ronald W. Davis","doi":"10.1080/02648725.2000.10647990","DOIUrl":"https://doi.org/10.1080/02648725.2000.10647990","url":null,"abstract":"Genome projects are producing sequence data at a very fast pace (http:// www.ncbi.nlni.nih.govlEntrez/Genomeforghtml). The discovery of the complete human genome sequence is only a few years away and a working draft with 90% coverage is promised to appear by the time of this publication (Strategy meeting on human genome sequencing, Cold Spring Harbor, 1999). In addition to the detailed sequence, biologists will receive a list of all 50-100,000 genes in the human genome and the challenge then turns towards organizing the genes and understanding how genes operate and interact to produce a living system. Traditional gene-by-gene analyses are inefficient for obtaining information about the function, regulation, and sequence variation of the thousands of genes in a genome. Highly parallel analyses are needed to be able to survey biology from a global perspective. One type of tool for studying biology from a global perspective is the high-density array, also known as a microarray, which consists of a miniaturized, high-density array of probes bound to a solid surface. Current applications have been based on DNA probes, although in theory other molecules such as proteins or small molecular weight compounds can also be arrayed at high density. Exploiting the specificity of hybridization, DNA probes on high-density arrays can detect the presence of individual target sequences in complex mixtures. This ability allows for massively parallel hybridization assays for large numbers of genes and sequences, and has been primarily applied to survey genomes for variations in mRNA expression levels or between DNA sequences. Using. high-density DNA arrays for mRNA expression studies, rapid, accurate, and","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"3 1","pages":"109 - 146"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75441117","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 13
Laser Reshaping of Cartilage 软骨激光整形术
Pub Date : 2000-08-01 DOI: 10.1080/02648725.2000.10648005
E. Sobol, A. Sviridov, A. Omel’chenko, V. Bagratashvili, M. Kitai, S. Harding, N. Jones, K. Jumel, M. Mertig, W. Pompe, Yuriy M. Ovchinnikov, A. Shekhter, Valerti Svistushkin
1Institute ofLaser and In/orlnation Technologies, Russian Acadetny of SciencesJ 142092 Troitsk. Russia, 2University ofNottillghal1l., NCMH ullit, School of Biological Sciences, Sutton BOllillgt01Z, Leics. LEJ2 5RD, U.K., JUniversity of Nottinghal1z. Division o.f Otorhinolaryngology, Queens Medical Centre, Nottillghal11. NG7 2UH, U.K., 4Technical University ofDresden, Institul fur Werkstoffivissellschaft, D-OJ062 Dresden, Gerl1lallY and 5Sec!teIl01' Medical Acadel1zy 0/Mosco}" Mosco·t.., J19881, Russia
1俄罗斯科学院激光与光学技术研究所,特罗伊茨克142092;2俄罗斯诺蒂尔哈尔大学;英国生物科学学院,英国萨顿堡生物科学学院,英国萨顿堡生物科学学院。lej25,英国,诺丁汉大学。女王医疗中心耳鼻咽喉科,诺丁汉。2 .德国德累斯顿工业大学,德国德累斯顿工业技术研究所,D-OJ062德国德累斯顿,Gerl1lallY和5Sec!teIl01' Medical academyzy 0/Mosco}" Mosco·t.. ", J19881,俄罗斯
{"title":"Laser Reshaping of Cartilage","authors":"E. Sobol, A. Sviridov, A. Omel’chenko, V. Bagratashvili, M. Kitai, S. Harding, N. Jones, K. Jumel, M. Mertig, W. Pompe, Yuriy M. Ovchinnikov, A. Shekhter, Valerti Svistushkin","doi":"10.1080/02648725.2000.10648005","DOIUrl":"https://doi.org/10.1080/02648725.2000.10648005","url":null,"abstract":"1Institute ofLaser and In/orlnation Technologies, Russian Acadetny of SciencesJ 142092 Troitsk. Russia, 2University ofNottillghal1l., NCMH ullit, School of Biological Sciences, Sutton BOllillgt01Z, Leics. LEJ2 5RD, U.K., JUniversity of Nottinghal1z. Division o.f Otorhinolaryngology, Queens Medical Centre, Nottillghal11. NG7 2UH, U.K., 4Technical University ofDresden, Institul fur Werkstoffivissellschaft, D-OJ062 Dresden, Gerl1lallY and 5Sec!teIl01' Medical Acadel1zy 0/Mosco}\" Mosco·t.., J19881, Russia","PeriodicalId":8931,"journal":{"name":"Biotechnology and Genetic Engineering Reviews","volume":"93 1","pages":"553 - 578"},"PeriodicalIF":0.0,"publicationDate":"2000-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79656881","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 98
期刊
Biotechnology and Genetic Engineering Reviews
全部 Acc. Chem. Res. ACS Applied Bio Materials ACS Appl. Electron. Mater. ACS Appl. Energy Mater. ACS Appl. Mater. Interfaces ACS Appl. Nano Mater. ACS Appl. Polym. Mater. ACS BIOMATER-SCI ENG ACS Catal. ACS Cent. Sci. ACS Chem. Biol. ACS Chemical Health & Safety ACS Chem. Neurosci. ACS Comb. Sci. ACS Earth Space Chem. ACS Energy Lett. ACS Infect. Dis. ACS Macro Lett. ACS Mater. Lett. ACS Med. Chem. Lett. ACS Nano ACS Omega ACS Photonics ACS Sens. ACS Sustainable Chem. Eng. ACS Synth. Biol. Anal. Chem. BIOCHEMISTRY-US Bioconjugate Chem. BIOMACROMOLECULES Chem. Res. Toxicol. Chem. Rev. Chem. Mater. CRYST GROWTH DES ENERG FUEL Environ. Sci. Technol. Environ. Sci. Technol. Lett. Eur. J. Inorg. Chem. IND ENG CHEM RES Inorg. Chem. J. Agric. Food. Chem. J. Chem. Eng. Data J. Chem. Educ. J. Chem. Inf. Model. J. Chem. Theory Comput. J. Med. Chem. J. Nat. Prod. J PROTEOME RES J. Am. Chem. Soc. LANGMUIR MACROMOLECULES Mol. Pharmaceutics Nano Lett. Org. Lett. ORG PROCESS RES DEV ORGANOMETALLICS J. Org. Chem. J. Phys. Chem. J. Phys. Chem. A J. Phys. Chem. B J. Phys. Chem. C J. Phys. Chem. Lett. Analyst Anal. Methods Biomater. Sci. Catal. Sci. Technol. Chem. Commun. Chem. Soc. Rev. CHEM EDUC RES PRACT CRYSTENGCOMM Dalton Trans. Energy Environ. Sci. ENVIRON SCI-NANO ENVIRON SCI-PROC IMP ENVIRON SCI-WAT RES Faraday Discuss. Food Funct. Green Chem. Inorg. Chem. Front. Integr. Biol. J. Anal. At. Spectrom. J. Mater. Chem. A J. Mater. Chem. B J. Mater. Chem. C Lab Chip Mater. Chem. Front. Mater. Horiz. MEDCHEMCOMM Metallomics Mol. Biosyst. Mol. Syst. Des. Eng. Nanoscale Nanoscale Horiz. Nat. Prod. Rep. New J. Chem. Org. Biomol. Chem. Org. Chem. Front. PHOTOCH PHOTOBIO SCI PCCP Polym. Chem.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
0
微信
客服QQ
Book学术公众号 扫码关注我们
反馈
×
意见反馈
请填写您的意见或建议
请填写您的手机或邮箱
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
现在去查看 取消
×
提示
确定
Book学术官方微信
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术
文献互助 智能选刊 最新文献 互助须知 联系我们:info@booksci.cn
Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。
Copyright © 2023 Book学术 All rights reserved.
ghs 京公网安备 11010802042870号 京ICP备2023020795号-1