Biotechnology E-Book

Rolf D. Schmid

• Herausgeber: Wiley-VCH
• Kategorie: Fachliteratur
• Sprache: Englisch
• Veröffentlichungsjahr: 2016

Seitenzahl: 725

Beschreibung

This sequal to the "Pocket Guide to Biotechnology and Genetic Engineering", now in a large format, is ideal for exam preparations as well as serving as a handy reference for professionals, offering a concise and readily understandable overview of all important topics in modern biotechnology and genetic engineering. The content has been completely updated and restructured to reflect recent trends and developments and to follow the teaching curricula of most academic courses. New entries include glycobiology, algae, epigenetics, pre- and probiotics as well as C-sources and synthetic biology. The textbook still contains entries on the key topics in fermentation, bioprocess engineering and enzyme technology, along with industrial applications of biotechnology, focusing on the fields of food and medicine. The basic terms of microbiology, biochemistry, genetic engineering and cell biology are explained via an attractive layout including full color plates and the corresponding explanatory text. The whole is rounded off by a section on agricultural and environmental topics, as well as safety and ethical aspects. The result is the number-one primer in biotechnology.

Leseprobe

Table of Contents

Cover

Title

Copyright

Preface to the 1st edition

Preface to the 2nd edition

Introduction

Introduction

Early developments

Biotechnology today

Microbiology

Viruses

Bacteriophages

Microorganisms

Bacteria

Yeasts

Fungi

Algae

Some bacteria of importance for biotechnology

Microorganisms: isolation, preservation, safety

Microorganisms: strain improvement

Biochemistry

Biochemistry

Amino acids, peptides, proteins

Enzymes: structure, function, kinetics

Sugars, glycosides, oligo- and polysaccharides

Lipids, membranes, membrane proteins

Metabolism

Genetic engineering

DNA: structure

DNA: function

RNA

Genetic engineering: general steps

Preparation of DNA

Other useful enzymes for DNA manipulation

PCR: general method

PCR: laboratory methods

DNA: synthesis and size determination

DNA sequencing

Transfer of foreign DNA in living cells (transformation)

Gene cloning and identification

Gene expression

Gene silencing

Epigenetics

Gene libraries and gene mapping

Genetic maps of prokaryotes

Genetic maps of eukaryotes

Metagenomics

Cell biology

Cell biology

Stem cells

Blood cells and immune system

Antibodies

Reporter groups

Solid state fermentation (SSF)

Growing microorganisms

Growth kinetics and product formation

Fed-batch, continuous and high cell density fermentation

Fermentation technology

Fermentation technology: scale-up

Cultivation of mammalian cells

Mammalian cell bioreactors

Enzyme and cell reactors

Recovery of bioproducts

Recovery of proteins: chromatography

Economic aspects of industrial processes

Food and food additives

Alcoholic beverages

Beer

Fermented food

Food and lactic acid fermentation

Prebiotics and probiotics

Bakers’ yeast and fodder yeasts

Fodder yeasts from petroleum feedstocks, single cell oil

Amino acids

L-Glutamic acid

D, L-Methionine, L-lysine, and L-threonine

Aspartame™, L-phenylalanine, and L-aspartic acid

Amino acids

via

enzymatic transformation

Vitamins

Nucleosides and nucleotides

Industrial products

Bio-Ethanol

1-Butanol

Higher alcohols and alkenes

Acetic acid/vinegar

Citric acid

Lactic acid, 3-hydroxy-propionic acid (3-HP)

Gluconic acid and “green” sugar chemicals

Dicarboxylic acids

Biopolymers: Polyesters

Biopolymers: Polyamides

Polysaccharides

Biosurfactants

Fatty acids and their esters

Enzyme technology

Biotransformation

Technical enzymes

Applied enzyme catalysis

Regio- and enantioselective enzymatic synthesis

Enzymes as processing aids

Detergent enzymes

Enzymes for starch hydrolysis

Enzymatic starch hydrolysis

Enzymes and sweeteners

Enzymes for the hydrolysis of cellulose and polyoses

Enzymes in pulp and paper processing

Pectinases

Enzymes and milk products

Enzymes in baking and meat processing

Other enzymes for food products and animal feed

Enzymes in leather and textile treatment

Procedures for obtaining novel technical enzymes

Protein design

Antibiotics

Antibiotics: occurrence, applications, mechanism of action

Antibiotics: screening, industrial production, and mechanism of action

Antibiotic resistance

β-Lactam antibiotics: structure, biosynthesis, and mechanism of action

β-Lactam antibiotics: manufacture

Amino acid and peptide antibiotics

Glycopeptide, lipopeptide, polyether, and nucleoside anti-biotics

Aminoglycoside antibiotics

Tetracyclines, chinones, chinolones, and other aromatic antibiotics

Macrolide antibiotics

New pathways to antibiotics

Pharmaceuticals and medical technology

Insulin

Growth hormone and other hormones

Hemoglobin, serum albumen, and lactoferrin

Blood clotting agents

Anticoagulants and thrombo-lytic agents

Enzyme inhibitors

Interferons

Interleukins and “anti-interleukins”

Erythropoietin and other growth factors

Other therapeutic proteins

Monoclonal and catalytic antibodies

Recombinant antibodies

Therapeutic antibodies

Vaccines

Recombinant vaccines

Steroid biotransformations

Diagnostic enzymes

Enzyme tests

Biosensors

Immunoanalysis

Glycobiology

Agriculture and environment

Animal breeding

Embryo transfer, cloned animals

Gene maps

Transgenic animals

Breeding, gene pharming and xenotransplantation

Plant breeding

Plant tissue surface culture

Plant cell suspension culture

Transgenic plants: methods

Transgenic plants: resistance

Transgenic plants: products

Aerobic wastewater treatment

Anaerobic wastewater and sludge treatment

Biological treatment of exhaust air

Biological soil treatment

Microbial leaching, biofilms, and biocorrosion

Megatrends

The human genome

Functional analysis of the human genome

Pharmacogenomics, nutrigenomics

DNA assays

Gene therapy

Induced pluripotent stem cells (iPS)

Tissue Engineering

Drug screening

High-throughput sequencing

Proteomics

DNA and protein arrays

Metabolic engineering

Synthetic biology

Systems biology

Bioinformatics: sequence and structural databases

Bioinformatics: functional analyses

Carbon sources (C-sources)

Biorefineries

Safety in genetic engineering

Regulation of products derived from biotechnology

Ethical considerations and acceptance

Patents in biotechnology

International aspects of biotechnology

Further Reading

Index

Picture Credits

End User License Agreement

Guide

Cover

Table of Contents

Begin Reading

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Rolf D. Schmid

Claudia Schmidt-Dannert

Biotechnology

An Illustrated Primer

171 color plates by Ruth Hammelehle

Authors:

Prof. Dr. Rolf D. SchmidBio4BusinessJagdweg 370569 StuttgartGermany

Prof. Dr. Claudia Schmidt-DannertUniversity of MinnesotaDepartment of Biochemistry1479 Gortner Ave140 Gortner LabSt. Paul, MN 55108USA

Graphic Designer:Ruth HammelehleMarktplatz 573230 Kirchheim unter TeckGermany

Cover:DNA helix from fotolia©A-Mihalis

All books published by Wiley-VCH are carefully produced. Nevertheless, authors, editors, and publisher do not warrant the information contained in these books, including this book, to be free of errors. Readers are advised to keep in mind that statements, data, illustrations, procedural details or other items may inadvertently be inaccurate.

Library of Congress Card No.:applied for

British Library Cataloguing-in-Publication DataA catalogue record for this book is available from the British Library.

Bibliographic information published by the Deutsche NationalbibliothekThe Deutsche Nationalbibliothek lists this publication in the Deutsche Nationalbibliografie; detailed bibliographic data are available on the Internet at <http://dnb.d-nb.de>.

© 2016 Wiley-VCH Verlag GmbH & Co. KGaA, Boschstr. 12, 69469 Weinheim, Germany

All rights reserved (including those of translation into other languages). No part of this book may be reproduced in any form – by photoprinting, microfilm, or any other means – nor transmitted or translated into a machine language without written permission from the publishers. Registered names, trademarks, etc. used in this book, even when not specifically marked as such, are not to be considered unprotected by law.

Print ISBN: 978-3-527-33515-2

Preface to the 1st edition

Biotechnology, a key technology of the 21st century, is more than other fields an interdisciplinary endeavor. Depending on the particular objective, it requires knowledge in general biology, molecular genetics, and cell biology; in human genetics and molecular medicine; in virology, microbiology, and biochemistry; in the agricultural and food sciences; in enzyme technology, bioprocess engineering, and systems science. And in addition, biocomputing and bioinformatics play an ever-increasing role. Against this background, it is of little surprise that few concise textbooks try to cover the whole field, and important applied aspects such as animal and plant breeding or analytical biotechnology are often missing even from multivolume monographs.

On the other hand, I have experienced during my own life-long studies, and also when teaching my students, how energizing it is to emerge occasionally from the thousands of details which must be learned, to look at a unifying view.

The Pocket Guide to Biotechnology and Genetic Engineering is an attempt to provide this kind of birds-eye perspective. Admittedly, it is daring to discuss each of this book’s topics, ranging from “Beer” to “Tissue Engineering” and “Systems Biology”, on a single text page, followed by one page of graphs and tables. After all, monographs, book chapters, reviews, and hundreds of scientific publications are devoted to each single entry covered in this book (many of them are provided in the literature citations). On the other hand, the challenge of surveying each entry in barely more than 4000 characters forces one to concentrate on the essentials and to put them into a wider perspective.

I hope that I have succeeded at least to some extent in this endeavor, and that you will find the clues to return safely from the highly specialized world of science, and its sophisticated terms, to your own evaluation of the opportunities and challenges that modern biotechnology offers to all of us.

This English version is not a simple translation of the original version, which was published in German in December, 2001, but an improved and enlarged second edition: apart from a general update of all data, it contains three new topics (Tissue Engineering, RNA, and Systems Biology).

At this point, my thanks are due to some people who have essentially contributed to this book. Above all, I wish to acknowledge the graphic talent of Ruth Hammelehle, Kirchheim, Germany, who has done a great job in translating scientific language into very clear and beautiful graphs. Marjorie Tiefert, San Ramon, California, has been more than an editor: she has caught and expressed the original spirit of this book. My thanks also to the publisher, in particular to Romy Kirsten. Special thanks are due to the many colleagues in academia and industry who have contributed their time and energy to read through the entries in their areas of expertise and provide me with most useful suggestions and corrections. These were: Max Roehr, University of Vienna; Waander Riethorst, Biochemie GmbH, Kundl; Frank Emde, Heinrich Frings GmbH, Bonn; Peter Duerre, University of Ulm; Edeltraut Mast-Gerlach, Ulf Stahl and Dietrich Knorr, Technical University Berlin; Udo Graefe, Hans-Knoell Institute, Jena; Jochen Berlin, GBF, Braunschweig; Allan Svenson, Novozymes A/S, Copenhagen; Helmut Uhlig, Breisach; Frieder Scheller, University of Potsdam; Bertold Hock, University of Munich-Weihenstephan; Rolf Blaich, Rolf Claus, Helmut Geldermann and Gerd Weber, University of Hohenheim; Hans-Joachim Knackmuss, Dieter Jendrossek, Karl-Heinrich Engesser, Joerg Metzger, Peter Scheurich, Ulrich Eisel, Matthias Reuss, Klaus Mauch, Christoph Syldatk, Michael Thumm, Joseph Altenbuchner, Paul Keller and Ulrich Kull, University of Stuttgart; Thomas von Schell, Stuttgart; Joachim Siedel, Roche AG, Penzberg; Rolf Werner and Kerstin Maier, Boehringer-Ingelheim, Biberach; Frank-Andreas Gunkel, Bayer AG, Wuppertal; Michael Broeker, Chiron Bering GmbH, Marburg; Bernhard Hauer and Uwe Pressler, BASF AG, Ludwigshafen; Frank Zocher, Aventis Pharma, Hoechst; Tilmann Spellig, Schering AG, Bergkamen; Akira Kuninaka, Yamasa Corporation, Chosi; Ian Sutherland, University of Edinburgh; Julia Schueler, Ernst & Young, Frankfurt. Among the many members of my institute in Stuttgart who have IX patiently helped me with the manuscript I wish to especially acknowledge Jutta Schmitt, Till Bachmann, Jürgen Pleiss and Daniel Appel.

In spite of all efforts and patient cross-checking, it would be a miracle if no unclearness or errors exist. These are entirely the author’s fault. I would be most grateful to all readers who will let me know, via the web address www.itb.unistuttgart.de/pocketguide, where this book can be further improved.

Rolf D. SchmidStuttgart, New Year 2002/2003

Preface to the 2nd edition

In the 10 years since the first edition of this booklet in English, the developments in biotechnology have further accelerated. This is true for the science, which has generated new methods such as synthetic biology, genome editing or high-throughput sequencing of genomes, generating big data which provide us with ever more detailed perceptions of the living world. New applications in industry have followed suit – in the medical sciences, eminent examples are the therapeutic antibodies, iPS-derived stem-cell technologies or a personalized medicine based on SNP analysis and companion diagnostics; in industrial biotechnology, the emerging concepts of a “bioeconomy” based on renewable resources such as biomass, waste or carbon dioxide provide certainly a megatrend. It goes without saying that a little booklet can only provide short sketches for each of these fields. An updated literature suvey attempts to compensate for this shortcoming.

It is my great joy that Professor Claudia Schmidt-Dannert, University of Minnesota, has accepted to join this and future editions as a co-author. This will help to keep the wide information provided in this book as updated as possible in a global setting.

Our sincere thanks go, beyond the individuals mentioned in the first edition, to numerous friends and colleagues who have helped again with their professional knowledge. Our particular appreciation goes to Wolfgang Wohlleben, Tuebingen University; Karin Benz, NMI Reutlingen; Ulrike Konrad, Protagen; Karl Maurer, ABEnzymes, Darmstadt; Bernhard Hauer, Georg Sprenger and Juergen Pleiss, Stuttgart University; Ulrich Behrendt, Munich; Dirk Weuster-Botz, Munich Technical University; Joern Kalinowsky, Bielefeld University; Vlada Urlacher, Düsseldorf University, and Frieder Scheller, Potsdam University.

The high quality of the artwork is due to Ruth Hammelehle, Kirchheim, of the final editing to Bernhard Walter, both of epline Co., Kirchheim u. T. Our deep thanks to both of them, to the editorial team, Dr Gregor Cicchetti, Dr Andreas Sendtko and Dr Claudia Ley at Wiley-VCH in Weinheim, Germany , and to Dr Sarah Perdue and Dr Bradford Condon at the University of Minnesota, St. Paul. The contribution of Dr Alexandra Prowald, who provided an excellent index to this book, is also highly appreciated.

Rolf D Schmid, Claudia Schmidt-Dannert Stuttgart, Germany and St. Paul, Minnesota, Summer 2015

Introduction

This pocket guide is written for students of biology, biochemistry and bioprocess engineering who are looking for a short introduction to the many different areas where modern biotechnologies are making an impact. It is also intended as a handy reference for teachers, patent attorneys, managers and investors seeking a quick, yet professional answer surrounding an upcoming topic of industrial biotechnology. To this end, specialized knowledge from a wide range of scientific disciplines has been condensed over a total of 171 color plates and further described on the accompanying text page, as well as complemented by a comprehensive survey of the literature. Cross-references provide additional help in jumping from technical applications of biotechnology, for example, to the fundamental science behind the application.

Completely updated and supplemented by many new topics, this second edition retains the modular format, but the structure of the book has been changed. It now begins, after a brief historical survey, with short introductions to the basic fields of modern biotechnology: microbiology, biochemistry, molecular genetics, cell biology and bioprocess engineering. It is only in the second part that the focus is on applications, such as food and food additives, industrial products, enzyme technology and, most comprehensively, the many contributions of biotechnology to the medical field, including the manufacture of antibiotics, biologicals such as antibodies, but also in medical technology. This section is rounded off with a description of the applications in agriculture, such as animal or plant breeding, and in environmental protection. The third section of the book deals with the current megatrends in the applied life sciences. These include genomics and such post-genomic trends as personalized medicine, with bioinformatics seen as an answer to current needs in big data processing, but also cell technology and gene therapy, as well as technologies devoted to building a new so-called bioeconomy, i. e. sustainable in energy and material use. The text ends with five chapters devoted to various aspects of safety and ethics, including patent and registration-related topics.

The objective of this book is to provide readers with a compact reference on the wide and expanding field of modern biotechnology. We hope that we succeeded not only in offering an attractive and stimulating read, but also in instigating in the reader the desire to dig deeper into this fascinating area of human endeavor.

Introduction

Early developments

History. The origins of what we call biotechnology today probably originated with agriculture and can be traced back to early history. Presumably, since the beginning people have gained experience on the loss of food by microbial spoilage; on food conservation by drying, salting, and sugaring; and on the effects of fermented alcoholic beverages. As the first city cultures developed, we find documents and drawings on the preparation of bread, beer, wine, and cheese and on the tanning of hides using principles of biotechnology. In Asia, fermented products such as Sauerkraut (China), Kimchi (Korea) or Gari (Indonesia) have been produced for thousands of years. In Europe, starting in the 6th century, the monasteries with their well organized infrastructure developed protocols for the arts of brewing, wine-making, and baking. We owe our strong, alcohol-rich stout beers to the pious understanding of the monks that “Liquida non fragunt ieiunum” (Liquors do not interfere with the chamfering time). Modern biotechnology, however, is a child of microbiology, which developed significantly in the late 19th century. The First and Second World Wars in the first half of the 20th century next probably provided the strongest challenge to microbiologists, chemists, and engineers to establish modern industrial biotechnology, based on products such as organic solvents and antibiotics. During and after this period, many ground-breaking discoveries and developments were made by biochemists, geneticists, and cell biologists and gave rise to molecular biology. At this point, the stage was set for modern biotechnology, based on genetic and cell engineering, to come into being during the 1970s and ’80s. With the advent of information technology, finally, modern biotechnologies gave rise to genomics, proteomics and cellomics, which promise to develop into the key technologies of the 21st century, with a host of applications in medicine, food and agriculture, chemistry and environmental protection.

Early pioneers and products. Biotechnology is an applied science – many of its developments are driven by economic motives. In 1864 Louis Pasteur, a French chemist, used a microscope for the first time to monitor the fermentation of wine vs. lactic acid. Using sterilized media (“pasteurization”), he obtained pure cultures of microorganisms, thus laying the foundation for applied microbiology and expanding this field into the control of pathogenic microorganisms. At the start of the 20th century, it occurred to the German chemist Otto Roehm and to the Japanese scientist Jokichi Takamine that enzymes isolated from animal wastes or from cultures of molds might be useful catalysts in industrial processes. Otto Roehm’s idea revolutionized the tanning industry, since tanning up to this time was done using dog excrements. In the field of public health, the introduction of biological sewage treatment around 1900 was a milestone for the prevention of epidemics. During World War I, Carl Neuberg in Germany and Chaim Weizmann, a Russian emigrant to Britain and of Jewish origin, developed large-scale fermentation processes for the preparation of ammunition components (glycerol for nitroglycerol and acetone for Cordite). The Balfour declaration and the ensuing foundation of the state of Israel, whose first president Weizmann became, is thus directly linked to an early success in biotechnology. In the postwar period, 1-Butanol, the second product from Weizmann’s Clostridium-based fermentation process, became highly important in the USA as a solvent for car paints. The serendipitous discovery of penicillin by Alexander Fleming (1922), much later turned into a drug by Howard Florey, initiated the large-scale production of penicillin and other antibiotics during World War II. As early as 1950, > 1000 different antibiotics had been isolated and were increasingly used in medicine, in animal feeds, and in plant protection. This was accompanied by a rising tide of antibiotic resistance, triggering research on the mechanisms of microbial defense mechanisms. Since 1950, the analytical use of enzymes, later of antibodies, began another important field of modern biotechnology. The first glucose biosensor was introduced by Leland C. Clark in 1954, initiating a concept for blood glucose monitoring which now commands a market of several billion US-$. In the shadow of the 1960s’ oil crises and the emerging awareness of overpopulation, the conversion of biomass to energy such as bio-ethanol and of single-cell protein from petroleum or methanol was developed. Now, in 2014, “biorefineries” are under active development.

Biotechnology today

Genetic Engineering and Cell Technology. In 1973, Stanley Cohen and Frederick Boyer in San Francisco were the first to express a designed foreign gene in a host organism. After about 10 years the first recombinant drug, human somatotropin, was registered. Since then, more than 50 genetically engineered proteins have been registered as therapeutic agents, including insulin (for diabetics), erythropoietin (for anemic patients), factor VIII (for hemophiliacs), interferon-β (for multiple sclerosis patients), recombinant antibodies and vaccines. Many hundred more are under development. Although the new technologies were first applied to medicine, their innovation potential in agriculture and food production soon began to emerge. Thus, transgenic crops were bred that were resistant to herbicides, insects, or viruses. Today, they are predominantly grown in North America. Flowers have been genetically modified to exhibit new colors, vegetables or fruits to show enhanced nutritive properties, and woods to contain less lignin for improved paper production. In the chemical industry, biopolymers, prepared from biomass-derived chemicals such as starch or cellulose, have begun to replace petrochemical products, and “biorefineries” have appeared which generate biofuels and chemicals from biomass. These technologies are changing the face of agriculture. High-throughput gene sequencers and supercomputers are making the sequencing of human genomes relatively cheap and routine, and genome-based information is now widely used to understand the molecular basis of diseases and to develop novel drugs by a target-oriented screening approach. Novel approaches, such as proteomics and structural biology, are contributing to our fundamental understanding of the chemistry of life and disease. Using gene therapy, we attempt to replace malfunctioning with correctly functioning genes. These developments are in step with great advances in cell biology, which focus on the complex interactions of cells in a multicellular organism. Human differentiated cells such as cardiomyocytes or neurons can now be obtained from embryonal stem cells or even from adult human cells by genetic reprogramming via induced pluripotent stem cells (iPS). Tissue engineering has become a surgical approach to repairing wounded tissue such as skin, bone or cartilage.

Public acceptance. The sheep Dolly, born in 1998, was the first animal ever cloned from a somatic cell of and thus identical to her mother. The thrust and possible consequences of such developments, e. g., for embryonic manipulations or individual (prenatal) genetic fingerprinting, have led to emotional public discussion. Typical subjects are: at what stage does human life begin and when does it need to be protected? Do we accept the cloning of humans? To which extent can we accept a deterministic view of individual health risks, e. g., by an employer or an insurance company? How will molecular genetics and gene therapy affect the age distribution in our societies? Is it ethical to genetically modify plants and animals at will? To what extent are such manipulations in harmony with the ecosystem and its natural diversity? How will the new biotechnologies influence the relationship of industrialized and developing economies? None of these questions has been completely resolved yet. As we begin to understand and interfere with the functions of the human brain, answering these questions on a global scale will become even more urgent.

Foundations. The body of this pocket guide is devoted to the many and growing applications of biotechnology, including discussion of today’s “megatrends” (2014), which include bioinformatics. In the introduction to this book, however, the multidisciplinary foundations of the field are briefly outlined. We start with microbiology, which is the oldest discipline and has led the way to many contemporary technologies. This is followed by biochemistry, the science of life’s building blocks, their metabolism and its regulation. A key property of life is to propagate. As a consequence, the basics of molecular genetics and genetic engineering will be presented. Cell biology and immunology continue to have a great impact on biotechnology, and some basics are introduced. Finally, without bioprocess engineering, a discipline mastered by engineers, the manufacturing of bioproducts could not be done in an economical way. It is obvious that the space available does not allow a thorough discussion of all these fields, but current literature will be provided to the reader interested in further reading.

Microbiology

Viruses

General. A virus is an infectious particle without indigenous metabolism. Its genetic program is written in either DNA or RNA, whose replication depends on the assistance of a living host cell. A virus propagates by causing its host to form a protein coat (capsid), which assembles with the viral nucleic acid (virus particle, nucleocapsid). Viruses can infect most living organisms; they are mostly host-specific or even tissue- or cell-specific. Viruses are classified by their host range, their morphology, their nucleic acid (DNA/RNA), and their capsids. In medicine and veterinary medicine, the early diagnosis, prophylaxis and therapy of viral human and veterinary diseases plays a crucial role. AIDS (HI virus), viral hemorrhagic fever (Ebola virus), avian flu (H5N1-, H7N9-virus) (→250) or hepatitis (several virus families) are important examples of viruses involved in human diseases, as are Rinderpest (Morbillivirus) or infectious salmon anemia (ISA virus) in epizootic veterinary diseases. In biotechnology, viruses are used for the development of coat-specific or component vaccines and for obtaining genetic vector and promoter elements which are, e. g., used in animal cell culture and studied for use in gene therapy.

Viruses for animal experiments. The first cloning experiments with animal cells were done in 1979, using a vector derived from simian virus 40 (SV40) (→98). This virus can infect various mammals, propagating in lytic or lysogenic cycles (lysis vs. retarded lysis of host cells). Its genome of ca. 5.2 kb contains early genes for DNA replication and late genes for capsid synthesis. Expression vectors based on SV40 contain its origin of replication (ori), usually also a promoter, and a transcription termination sequence (polyA) derived from the viral DNA. For the transfection of mouse cells, DNA constructs based on bovine papilloma virus (BPV) are preferred. In infected cells, they change into multicopy plasmids which, during cell division, are passed on to the daughter cells. Attenuated viruses derived from retro, adeno, and herpes viruses are being investigated as gene shuttles for gene therapy (→304). Retroviruses, e. g., the HI virus, contain an RNA genome. They infect only dividing cells and code for a reverse transcriptase which, in the host cell, transcribes the RNA into cDNA. HIV-cDNA is then integrated into the host genome where it directs, via strong promoters, the formation of viral nucleic acid and capsid proteins. Some hundred experiments with retroviral vectors having replication defects have already been carried out for gene therapy. A disadvantage of using retroviral vectors lies in their small capacity to package foreign DNA (inserts), whereas vectors derived from adenoviruses can accommodate up to 28 kb of inserted DNA. In contrast to retroviruses, adenoviruses can infect non-dividing cells, but their DNA does not integrate into the host chromosomal DNA. For gene therapy targeted to neuronal cells, e. g., in experiments related to Alzheimer’s or Parkinson’s disease, -derived vectors are often used. Their large genome of 152 kb allows them to accommodate inserts > 20 kb of foreign DNA. A similar insert size is reached with Vaccina viruses, which may infect a wide range of cell types.