Production of biopharmaceuticals, antibodies and edible vaccines in transgenic plants

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Current Studies of Biotechnology – Volume IV. – Immuno-Modulatory Drugs

SIBILA JELASKA1*, SNJEŽANA MIHALJEVIĆ2, NATAŠA BAUER1 1 Faculty of Science, Department of Molecular Biology, University of Zagreb, Zagreb, Croatia 2 Institute Ruđer Bošković, Zagreb, Croatia

ABSTRACT The use of plants and otherbotanicals as a source of medicines exists of the earliest stages of civilization. Despite great advances in synthetic organic chemistry, it is estimated that about onefourth of present day prescription drugs still have a botanical origin. Recently, and through modern biotechnology, there has been a revival of interest in obtaining new pharmaceuticals from botanical sources. Through geneticmodification, it is now recognized that plants are potentially a new source of pharmaceutical proteins including vaccines, antibodies, blood substitutes and other therapeutic entities. Unlike mammalian-derived rDNA drugs, plant-derived antibodies, vaccines and other proteins are particularly advantageous since they are free of mammalian viral vectors and human pathogens. Advantages offered by plants includealso low cost of cultivation and high biomass production, relatively fast “gene to protein” time, low capital and operating costs, excellent scalability, eukaryotic posttranslational modifications and a relatively high protein yield. Key words: Heterologous proteins, plant-made pharmaceuticals, edible vaccine, molecular farming

INTRODUCTION Plants have provided humans with useful molecules formany centuries, but only in the past 20 years has it become possible to use plants for the production of specific heterologous proteins (1). The first pharmaceutically relevant protein made in plants was human growth hormone, which was expressed in transgenic tobacco in 1986 (2). Since then, many other human proteins have been produced in an increasingly diverse range of crops. In 1989, the firstantibody was expressed in tobacco (3), which showed that plants could assemble complex functional glycoproteins with several subunits. The structural authenticity of plant-derived recombinant proteins was confirmed in 1992, when plants were used for the first time to produce an experimental vaccine: the hepatitis B virus (HBV) surface antigen (4). More recently, the range of recombinant proteinsmade in plants has extended to include industrial enzymes (5), technical proteins that are used in research (6), milk proteins that are suitable nutritional supplements (7), and new protein polymers with both medical and industrial uses (8).

* Author address: Prof.dr. Sibila Jelaska, Faculty of Science, Department of Molecular Biology, University of Zagreb, Horvatovac 102 a, 10000 Zagreb,Croatia; E-mail:



MOLECULAR FARMING SYSTEMS Molecular farming, biopharming, greening of vaccine technology and plant molecular farming are expressions for the large-scale production of recombinant proteins in living cells or organisms; frequently applied to the use of crop plants (or domestic animals) as expression hosts because of the allusion toagriculture. There are four methods of protein production from plants: a) stable nuclear transformation of a crop species that are grown in the field or a greenhouse, b) stable plastid transformation of a crop species, c) transient transformation of a crop species by agroinfiltration, and d) stable transformation of a plant species that is grown hydroponically or in in vitro systems so that thetransprotein is secreted into the medium and recovered (9). A detailed comparison of the economics, processing and regulatory constraints associated with the most common plant production systems is reviewed (10). Table 1 shows advantages and disadvantages of the above mentioned systems. Different plant species and their parts are used in recombinant protein production (tab. 2). Many of the early,...
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