• Rezultati Niso Bili Najdeni

Številne potencialne negativne učinke na okolje in zdravje živali se lahko z različnimi metodami zmanjša oz. prepreči. Potencialna varnostna tveganja se lahko zmanjša z izbiro ustreznih ekspresijskih platform, ki imajo sposobnost ustreznih post-translacijskih modifikacij in ne producirajo toksinov. Prenosu transgenov v okolje preko peloda se lahko izognemo z uporabo kloroplastne transformacije, kjer se transgen vstavi v kloroplastni genom, kloroplastna DNA pa se deduje maternalno, zato se transgen ne bo nahajal v pelodu (Guan in sod., 2013). Pobiranje listov gensko spremenjene rastline s pomočjo kloroplastne transformacije pred cvetenjem prepreči tudi ''uhajanje'' transgena v okolje preko semen (Shahid in Daniell, 2016). Smiselno je tudi uporabljati rastline, ki imajo možnost vegetativnega razmnoževanja, saj se s tem zmanjša tveganje za križanje z ne-transgenimi rastlinami na prostem (Liew in Hair-Bejo, 2015). Poleg tega se lahko določene rastline za pridobivanje cepiv goji tudi v rastlinjakih in drugih zaprtih prostorih in se s tem zmanjša možnost prenosa genskega materiala na ne-transgene rastline, lahko pa se aktivne komponente za cepiva pridobiva s pomočjo in vitro kultur.

Razvija se tudi nove napredne metode za zmanjšanje potencialnih negativnih vplivov na okolje, kot je npr. tehnika odstranjevanja eksogenega gena. Gre za posebno tehniko, pri kateri se v tarčne transgene rastline vstavi poseben gen pod kontrolo promotorja DNA regulatornega fragmenta. Vstavljeni posebni gen nato spontano odstrani eksogeni gen ob določenem času ali na določenem mestu v rastlini. Tako pelod, plodovi in semena transgenih rastlin ne vsebujejo transgena. S pomočjo te tehnike se lahko iz gensko spremenjenih rastlin po določeni razvojni fazi pridobiva ne-transgene rastline (Guan in sod., 2013).

7 ZAKLJUČEK

Kljub intenzivnim raziskavam, ki potekajo že več kot 20 let, veterinarska cepiva iz transgenih rastlin še vedno niso dosegla trga, vendar novi napredki na tem področju dajejo upanje, da se

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bo to zgodilo že v bližji prihodnosti. Razvita tehnologija je učinkovita, količine sintetiziranih rekombinantnih proteinov so dovolj velike, stestiranih je bilo že veliko cepiv za zelo različne patogene, obstajajo nove tehnike za povečanje varnosti takšnih cepiv in regulatorni organi so končno pripravljeni sprejeti idejo cepiv, pridobljenih iz transgenih rastlin. Takšna veterinarska cepiva bi predvsem v živinorejski proizvodnji bistveno olajšala proces cepljenja in znižala stroške zaradi enostavnejšega shranjevanja in transporta cepiva, zaradi česar bi bila cepiva dostopnejša. To je še posebej pomembno za države v razvoju, kjer se trenutno živalske bolezni širijo veliko hitreje kot v razvitejših državah ravno zaradi vseh pomanjkljivosti cepiv, ki se trenutno uporabljajo za nadzor nad živalskimi boleznimi. Omejitev širjenja živalskih bolezni bi doprinesla tako k blaginji živalske kot tudi človeške populacije.

8 VIRI

Aguirreburualde M. S. P., Gómez M. C., Ostachuk A., Wolman F., Albanesi G., Pecora A., Odeon A., Ardila F., Escribano J. M., Dus Santos M. J., Wigdorovitz A. 2013. Efficacy of a BVDV subunit vaccine produced in alfalfa transgenic plants. Veterinary Immunology and Immunopathology, 151, 3-4: 315-324

An C. H., Nazki S., Park S. C., Jeong Y. J., Lee J. H., Park S. J., Khatun A., Kim W. I., Park Y. I., Jeong J. C., Kim C. Y. 2018. Plant synthetic GP4 and GP5 proteins from porcine reproductive and respiratory syndrome virus elicit immune responses in pigs. Planta, 247, 1: 973–985

Baltes N. J., Gil-Humanes J., Voytas D. F. 2017. Chapter One - Genome engineering and agriculture: Opportunities and challenges. Progress in Molecular Biology and Translational Science, 149, 1: 1-26

Berinstein A., Vazquez-Rovere C., Asurmendi S., Gómez E., Zanetti F., Zabal O., Tozzini A., Conte Grand D., Taboga O., Calamante G., Barrios H., Hopp E., Carrillo E. 2005. Mucosal and systemic immunization elicited by Newcastle disease virus (NDV) transgenic plants as antigens. Vaccine, 23, 48-49: 5583-5589

Ceballo Y., Lopez A., Tiel K., Hernandez A. 2018. Plant-produced avian influenza antigens.

V: Prospects of Plant-Based Vaccines in Veterinary Medicine. MacDonald J. (ur.).

Springer, Cham: 189-208

Chan H. T., Daniell H. 2015. Plant-made oral vaccines against human infectious diseases - Are we there yet? Plant Biotechnology, 13, 8: 1056-1070

FDA. 2020. Get the Facts About Listeria. U.S. Food and Drug Administration.

https://www.fda.gov/ (20. apr. 2021)

Fischer R., Stoger E., Schillberg S., Christou P., Twyman R. M. 2004. Plant-based production of biopharmaceuticals. Current Opinion in Plant Biology, 7, 2: 152-158

Ganar K., Das M., Sinha S., Kumar S. 2014. Newcastle disease virus: Current status and our understanding. Virus Research, 184, 1: 71-81

19

Guan Z. J., Guo B., Huo Y. L., Guan Z. P., Dai J. K., Wei Y. H. 2013. Recent advances and safety issues of transgenic plant-derived vaccines. Applied Microbiology and Biotechnology, 97, 7: 2817–2840

Hahn B.S., Jeon I. S., Jung Y. J., Kim J. B., Park J. S., Ha S. H., Kim K. H., Kim H. M., Yang J. S., Kim Y. H. 2007. Expression of hemagglutinin-neuraminidase protein of Newcastle disease virus in transgenic tobacco. Plant Biotechnology Reports, 1, 1: 85–92

Hu J., Ni Y., Dryman B. A., Meng X. J., Zhang C. 2012. Immunogenicity study of plant-made oral subunit vaccine against porcine reproductive and respiratory syndrome virus (PRRSV). Vaccine, 30, 12: 2068-2074

Hugh-Jones M. E. 2015. Overview of Anthrax. MSD Veterinary Manual.

https://www.msdvetmanual.com/ (20. apr. 2021)

Jayalakshmi K., Paramasivam M., Sasikala M., Tamilam T. V., Sumithra A. 2017. Review on antibiotic residues in animal products and its impact on environments and human health.

Journal of Entomology and Zoology Studies, 5, 3: 1446-1451

Joensuu J. J., Niklander-Teeri V., Brandle J. E. 2008. Transgenic plants for animal health:

plant-made vaccine antigens for animal infectious disease control. Phytochemistry Reviews, 7, 1: 553–577

Jung M., Shin Y. J., Kim J., Cha S. B., Lee W. J., Shin M. K., Shin S. W., Yang M. S., Jang Y. S., Kwon T. H., Yoo H. S. 2014. Induction of immune responses in mice and pigs by oral administration of classical swine fever virus E2 protein expressed in rice calli.

Archives of Virology, 159, 1: 3219-3230

Kamel M., El-Sayed A., Castañeda Vazquez H. 2019. Foot-and-mouth disease vaccines:

recent updates and future perspectives. Archives of Virology, 164, 1: 1501-1513

Koya V., Moayeri M., Leppla S. H., Daniell H. 2005. Plant-based vaccine: Mice immunized with chloroplast-derived anthrax protective antigen survive anthrax lethal toxin challenge.

Infection and Immunity, 73, 12: 8266-8274

Kurup V. M., Thomas J. 2020. Edible vaccines: Promises and challenges. Molecular Biotechnology, 62, 2: 79–90

Lee G., Na Y. J., Yang B. G., Choi J. P., Seo Y. B., Hong C. P., Yun C. H., Kim D. H., Sohn E. J., Kim J. H., Sung Y. C., Kim Y. K., Jang M. H., Hwang I. 2014. Oral immunization of haemaggulutinin H5 expressed in plant endoplasmic reticulum with adjuvant saponin protects mice against highly pathogenic avian influenza A virus infection. Plant Biotechnology Journal, 13, 1: 62-72

Lentz E. M., Segretin M. E., Morgenfeld M. M., Wirth S. A., Dus Santos M. J., Mozgovoj M.

V., Wigdorovitz A., Bravo-Almonacid F. F. 2010. High expression level of a foot and mouth disease virus epitope in tobacco transplastomic plants. Planta, 231, 2: 387-395 Liew P. S., Hair-Bejo M. 2015. Farming of plant-based veterinary vaccines and their

applications for disease prevention in animals. Advances in Virology, 2015: 1-12

Loza-Rubio E., Rojas-Anaya E. 2014. Edible rabies vaccines. V: Commercial Plant-Produced Recombinant Protein Products. Howard J., Hood E. (ur.). Berlin, Springer: 153-177

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Loza-Rubio E., Rojas-Anaya E., Lopez J., Olivera-Flores M.T., Gomez-Lim M., Tapia-Perez G. 2010. Induction of a protective immune response to rabies virus in sheep after oral immunization with transgenic maize, expressing the rabies virus glycoprotein. Vaccine, 30, 37: 5551-5556

Mason H. S., Haq T. A., Clements J. D., Arntzen C. J. 1998. Edible vaccine protects mice against Escherichia coli heat-labile enterotoxin (LT): potatoes expressing a synthetic LT-B gene. Vaccine, 16, 13: 1336-1343

Massa S., Paolini F., Marino C., Franconi R., Venuti A. 2019. Bioproduction of a therapeutic vaccine against human papillomavirus in tomato hairy root cultures. Frontiers in Plant Science, 10, 452: 1-15

McGarvey, P., Hammond, J., Dienelt, M., Hooper D. C., Fu Z. F., Dietzschold B., Koprowski H., Michaels F. H. 1995. Expression of the rabies virus glycoprotein in transgenic tomatoes. Nature Biotechnology, 13, 1: 1484–1487

Meyers A. 2018. Diseases with Limited Research of Plant-Based Vaccines. V: Prospects of plant-based vaccines in veterinary medicine. MacDonald J. (ur.). Ontario, Western University: 347–367

Molina A., Hervás-Stubbs S., Daniell H., Mingo-Castel A. M., Veramendi J. 2004. High-yield expression of a viral peptide animal vaccine in transgenic tobacco chloroplasts. Plant Biotechnoly Journal, 2, 2: 141-153

Molina A., Veramendi J., Hervás-Stubbs S. 2005. Induction of neutralizing antibodies by a tobacco chloroplast-derived vaccine based on a B cell epitope from canine parvovirus.

Virology, 342, 2: 266-275

Nelson G., Marconi P., Periolo O., La Torre J., Alvarez M. A. 2012. Immunocompetent truncated E2 glycoprotein of bovine viral diarrhea virus (BVDV) expressed in Nicotiana tabacum plants: a candidate antigen for new generation of veterinary vaccines. Vaccine, 30, 30: 4499-4504

Ohya K., Matsumura T., Itchoda N., Ohashi K., Onuma M., Sugimoto C. 2005. Ability of orally administered ifn-α-containing transgenic potato extracts to inhibit Listeria monocytogenes infection. Journal of Interferon & Cytokine Research, 25, 8: 459-466 Ortigosa S. M., Fernández-San Millán A., Veramendi J. 2010. Stable production of peptide

antigens in transgenic tobacco chloroplasts by fusion to the p53 tetramerisation domain.

Transgenic Research, 19, 4: 703-709

Phan H. T., Pham V. T., Ho T. T., Pham N. B., Chu H. H., Vu T. H, Abdelwhab E. M., Scheibner D., Mettenleiter T. C., Hanh T. X., Meister A., Gresch U., Conrad U. 2020.

Immunization with plant-derived multimeric H5 hemagglutinins protect chicken against highly pathogenic avian influenza virus H5N1. Vaccines, 8, 4: 593

Polkinghorne I., Hamerli D., Cowan P., Duckworth J. 2005. Plant-based immunocontraceptive control of wildlife—“potentials, limitations, and possums”. Vaccine, 23, 15: 1847-1850

Rao J. P., Agrawal P., Mohammad R., Rao S . K., Reddy G. R., Dechamma H. J., S Suryanarayana V. V. 2012. Expression of VP1 protein of serotype A and O of

foot-and-21

mouth disease virus in transgenic sunnhemp plants and its immunogenicity for guinea pigs.

Acta Virologica, 56, 2: 91-99

Rivera A. L., Gómez-Lim M., Fernández F., Loske A. M. 2012. Physical methods for genetic plant transformation. Physics of Life Reviews, 9, 3: 308-345

Rybicki E. 2018. History and promise of plant-made vaccines for animals. V: Prospects of Plant-Based Vaccines in Veterinary Medicine. 2018. MacDonald J. (ur.). Springer, Cham:

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Schillberg S., Zimmermann S., Voss A., Fischer R. 1999. Apoplastic and cytosolic expression of full-size antibodies and antibody fragments in Nicotiana tabacum. Transgenic Research, 8, 4: 255-623

Shahid N., Daniell H. 2016. Plant‐based oral vaccines against zoonotic and non‐zoonotic diseases. Plant Biotechnology Journal, 14, 11: 2079-2099

Shahid N., Samiullah T. R., Shakoor S., Latif A., Yasmeen A., Azam S., Shahid A. A., Husnain T., Rao A. Q. 2020. Early stage development of a Newcastle disease vaccine candidate in corn. Frontiers in Veterinary Science, 7, 499: 1-12

Shao H. B., He D. M., Qian K. X., Shen G. F., Su Z. L. 2008. The expression of classical swine fever virus structural protein E2 gene in tobacco chloroplasts for applying chloroplasts as bioreactors. Comptes Rendus Biologies, 331, 3: 179-184

Skarjinskaia M., Ruby K., Araujo A., Taylor K., Gopalasamy-Raju V., Musiychuk K., Chichester J. A., Palmer G. A., de la Rosa P., Mett V., Ugulava N., Streatfield S. J., Yusibov V. 2013. Hairy roots as a vaccine production and delivery system. V:

Biotechnology of Hairy Root Systems, Doran P. M. (ur). Berlin, Springer: 115-134

Streatfield S. J., Lane J. R., Brooks C. A., Barker D. K., Poage M. L., Mayor J. M., Lamphear B. J., Drees C. F., Jilka J. M., Hood E. E., Howard J. A. 2003. Corn as a production system for human and animal vaccines. Vaccine, 21, 7-8: 812-815

Takeyama N., Kiyono H., Yuki Y. 2015. Plant-based vaccines for animals and humans: recent advances in technology and clinical trials. Therapeutic Advances in Vaccines and Immunotherapy, 3, 5-6: 139-154

UK Government. 2014. Newcastle disease: how to spot and report it. Department for Environment, Food & Rural Affairs and Animal and Plant Health Agency.

https://www.gov.uk/ (20. apr. 2021)

Yang Z. Q., Liu Q. Q., Pan Z. M., Yu H. X., Jiao X. A. 2007. Expression of the fusion glycoprotein of Newcastle disease virus in transgenic rice and its immunogenicity in mice.

Vaccine, 8, 4: 591-598

Zagorskaya A. A., Deineko E. V. 2017. Suspension-cultured plant cells as a platform for obtaining recombinant proteins. Russian Journal of Plant Physiology, 62, 6: 795-807 Zhang H., Liu M., Li Y., Zhao Y., He H., Yang G., Zheng C. 2010. Oral immunogenicity and

protective efficacy in mice of a carrot-derived vaccine candidate expressing UreB subunit against Helicobacter pylori. Protein Expression and Purification, 69, 2: 127-131

22 ZAHVALA

Iskreno se zahvaljujem mentorici izr. prof. dr. Zlati Luthar za pomoč pri izbiri tematike diplomske naloge, za prijaznost, stalno razpoložljivost in nasvete pri pisanju naloge.

Svoji družini in fantu, ki so me med pisanjem naloge spodbujali in mi svetovali, se iz srca zahvaljujem za podporo, ki mi jo vsakodnevno izkazujejo na vseh življenjskih področjih in verjamejo vame bolj kot jaz sama.

Zahvaljujem se tudi Brinu, moji antistresni bunkici, saj mi je med pisanjem naloge vedno delal družbo in bil moja moralna podpora v stresnih trenutkih.