Molecular Pharming: a Brief Overview
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JOURNAL OF AGRICULTURAL, BIOLOGICAL AND ENVIRONMENTAL SCIENCES Journal homepage: www.jakraya.com/journal/jabes REVIEW ARTICLE Molecular Pharming: A Brief Overview S.S. Pany a* and N.N. Mohanty b aDepartment of Veterinary Microbiology, College of Veterinary Science, Guru Angad Dev Veterinary and Animal Sciences University, Ludhiana-141004, bDivision of Veterinary Virology, IVRI, Mukteswar-263138, Nainital, Uttarakhand, India. Abstract Molecular pharming is a recent technology used for the cost *Corresponding Author: effective production of large quantities of proteins bearing therapeutic value S.S. Pany in transgenic plants and animals. It is advantageous over the traditional microbial and cell culture systems which are cumbersome and costly to Email: [email protected] handle and maintain, difficult to scale up and isolate the desired purified product. Pharming employs introduction of desired gene into animal or plant genome by microinjection or transformation respectively. Although Received: 30/09/2015 issues such as of food contamination and high cost of cloning circle around it, animal and plant pharming is the answer to rising demand of therapeutics Revised: 20/10/2015 required for control and prevention of various infectious and non infectious diseases in developing nations. Accepted: 21/10/2015 Keywords : Pharming, Animal model, Plant model, Therapeutic Transgenic. 1. Introduction was costly and cumbersome. Moreover the prevision of The world that we see today has transcended growing demands for affordable and safe drugs hinted way beyond many rough tides and stands before us researchers to explore new alternatives. Gradually it with a vast expanse for growth, development and was deduced that plants were capable of expressing exploration. Of the various facets contributing towards complex proteins after successful expression of global modernization, health sector plays a pivotal role. functional antibodies in transgenic plants. This brief Health sector has also undergone relative review aims at providing an overall concept of transformation in order to fulfil the growing demands molecular pharming in plants and animals and of the ever growing society. But this huge insistence enlightens on the scope that pharming holds for future. hangs over the sector like the ‘Sword of Damocles’ with anticipation of probable incompetence towards 2. History meeting the future challenges. The word pharming in The history of pharming dates back to 1990s simpler words can be described as cultivation of when human serum albumin was produced for the first therapeutics in a host of plants and animals (Norris, time by using transgenic tobacco and potato plant 2005) with genetic engineering and biotechnology (Sijmons et al., 1990). The concept was fortified by the serving as two essentials tools for its execution. It isn’t early 2000s with production of therapeutics, a new terminology to be discussed but a boulevard of recombinant enzymes, human and veterinary vaccines opportunity for researcher and scientists to harness the (Twyman et al., 2003). Gradually leading biotech power of genes for the benefit of society. With the companies ventured into the arena sprouting completion of human genome project many genes with miraculous results for several clinical conditions like therapeutic targets have been identified. The organism cystic fibrosis and non hodgkins lymphoma (Ma et al., into which the new genetic information is incorporated 2003). is referred to as expression system (Elbehri, 2005). Till date several expression systems have been explored but 3. Pharming in Mammals an ideal expression system must be cost effective, The advent of automated gene sequencing and convenient in storage and distribution of desired advancement in field of biotechnology has provided an product (Daniell et al. , 2001). Since decades microbial easy passage for evolution of pharming. Moreover system have been exploited for expression of exploiting the biological advantage of mammalian therapeutic proteins but the entire production set up system for achieving the desired goal has generated a Journal of Agricultural, Biological and Environmental Sciences | Year-2015 | Volume 02 | Pages 36-39 © 2015 Jakraya Pany and Mohanty…Molecular Pharming: A Brief Overview magnitude of possibilities to be explored. The current therapeutics and associated molecules, called technique of production of biologicals is an up- collectively as plant made pharmaceuticals (PMPs). gradation of the traditional method of using transgenic The technology used are production of stable nuclear bacteria, yeast and animal cells to meet the desired transgenic plants, transplastomic plants, transient ends. However the conventional techniques were expression using a plant virus (Tobacco Mosaic Virus) haunted by several shortcomings such as lack of cost and transient expression via Agrobacterium infiltration effectiveness, difficulty in isolation and purification of (Floss et al ., 2007). Most commonly, target DNA with products, use of complex machinery for maintenance, genetic information necessary to make the and difficulty in large scale production. pharmaceutical is transformed into the plant virus or So in order to combat the future demand of Agrobacterium or into plant genome directly which is biologicals many theoretical systems were proposed decoded by the plant’s protein-making machinery to like blood, egg white, seminal plasma, and urine but produce along with other plant proteins large quantities even they could not turn up with satisfactory results. of pharmaceutically active substances like a bioreactor. For example several studies by 2012 had shown that Several species such as Lemana minor and blood cannot store high levels of stable recombinant Physcomitrella patens have served as candidate for the proteins (Figueiredo and Blaszczyk, 2014). So, of all purpose. The plants could be grown in bioreactors and the mammalian systems studies milk emerged as the the target product being made to be produced in most efficient system for production and purification of secretory form, thus substantially reducing the burden recombinant proteins and biopharmaceuticals of protein purification (Büttner-Mainik et al ., 2011; (Houdebine et al ., 2009). Expression in the milk of a Gasdaska et al., 2003; Baur et al., 2005) and mammal, such as a cow, sheep, or goat, is a common additionally human pattern of glycosylation of proteins application and its abundance and flexibility of use in provides an edge over the conventional methodologies our day to day life makes it more suitable. The (Cox et al., 2006; Decker et al ., 2007). Arabdopsis is a transgenic animals with the ability to produce frequently studied model for expression purposes with biopharmaceuticals in milk are produced typically actual models being rice, maize, potato, tobacco and using pronuclear micro injection method followed by safflower. The risk of pharma crops entering the food using cloning technology to create additional offspring chain due to human error is a thought provoking issue that carry favourable modified genome (Dove, 2000). but despite the latent threat corn and soy beans are the Animals, compared to cell culture naturally harbour most common targets for field trials. Some examples of cellular infrastructure to produce complex proteins. plant pharming are antibody developed against Moreover animals are used as bioreactors minimise raw Streptococcus mutans caused human tooth decay in material, capital equipment, and maintenance costs tobacco, soyabean humanised anti-Herpes Simplex needed for conventional methods which in turn Virus (HSV) antibody against vaginal HSV minimise unit production cost per protein. Animal transmission in mice and carcino-embryonic antigen in bioreactors cost-effectively produce therapeutic rice and wheat, used in therapy against cancer in proteins for treatment of diseases like cystic fibrosis, humans (Daniell et al. , 2001), Foot and Mouth Disease haemophilia, osteoporosis, arthritis, malaria, HIV and virus (FMDV) Polyprotein P1 and protease 3C in monoclonal antibodies. A pig engineered with a Alfalfa, FMDV Structural protein VP1 (VP21 epitope) phytase gene in its salivary glands for better utilization fused to hepatitis B core protein (HBcAg) in tobacco, of phosphorus in feedstuffs in order to resolve animal Rabies virus surface glycoprotein G in tobacco, New waste issue called ‘enviro pig’ is the brainchild of Castle Disease Virus (NDV) Fusion (F) and animal pharming. Another bright example of successful Haemagglutinin (HA) protein in potato leaves (Floss et use of this technology was the production of ATryn, an al ., 2007). As compared to animal or microbial cell antithromin protein from milk of genetically modified cultures wherein scaling up of production and goats which got marketing approval from USDA in the purification of proteins was once a costly and complex year 2009. Some drawbacks revolving around animal affair, producing pharmaceuticals in plants is easy and pharming are safety of the food supply, safety of the efficient with 80% lesser costs required for pharmaceutical product, and keeping the transgenic out maintenance, safety, storage, time and distribution. of non-transgenic animals (Biotechnology Regulatory Plant expression systems also outrun traditional Services Factsheet : US Department of Agriculture; microbes in their ability to produce and assemble large 2006). quantities of complex proteins such as antibodies, hormones, enzymes, interleukins, blood proteins and