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Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

Impact of Genetically Modified on Human Health

Muhammad faisal1, Muhammad Saeed1, Misbah Aslam1 & Muhammad Asif Raheem1*

1*Institute of Molecular Biology & Biotechnology, Bahauddin Zakariya University, Multan-60880, Pakistan.

Article Received: 21 February 2019 Article Accepted: 15 July 2019 Article Published: 30 August 2019

ABSTRACT

Any nutritious substance that people or animals eat or drink or those plants absorb in order to maintain life and growth is called Food. With the huge increasing population of the world, food production from natural resources could not meet their needs. So researchers move to produce more food using molecular-level techniques. This type of food is called genetically modified food (GM food), whose genetic material has been altered which is not present already in nature. GM food is made to increase nutrient content by alternation, has many advantages for humans as it increases the nutritional content and formation of pest, drought, herbicide, and cold resistant plants. But at the same time, it has negative impacts also. It is genetically unsafe, causing organ damage and allergic reactions in the digestive tract. The researchers are trying to do their best to produce crops with their desired characteristics by using molecular-level techniques. Keywords: Genetically modified organisms, Transformation, Food crops, Bacillus thuringiensis.

INTRODUCTION

Abbreviation

GMOs: Genetically modified organisms

B.t.: Bacillus thuringiensis

CRISPR: Clustered regularly interspaced short palindromic repeats

FDA: Food and Drug Administration

INTRODUCTION

Genetically modified organisms (GMOs) are those organisms in which the genetic material has been altering which are not already present in nature and genetically modified are those foods derived from animals and the plants in which genes from particularly desired characteristics are added to an organism DNA. 1 GMOs are used in various ways such as used in biological and medical research, production of pharmaceutical drugs, experimental medicine, and agricultural field. By the gene alteration method, we are improving the needs of food and also it improves the quality of the food.2 We can get our desired characters or goals in plants and animals (such as resistance to disease, improve shelf life) more quickly as compared to using traditional methods. (Verma 2011) But many ethical issues are also opened which describe the negative effect of the production of genetically modified foods. It shows that the insertion of the gene of interest for desired characters in the food may be protective but may cause high expression of such genes related to many diseases such as chronic.4

METHODS OF PRODUCTION OF GM FOODS

Several methods are known for the production of GMOs from which we get the food. The gene of interest which inserted into the cell of , plants or animals is called a transgene. It is consolidated into the genome of the recipients which are called transgenic. The transgenes are genes with known traits or mutated variants of known genes. There many direct and indirect methods of gene transformation are known these days. 1,5

75 | P a g e ISSN (Online): 2582- 0974 Website: www.mejast.com

Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

PHYSICAL METHODS

S.No

1. Microinjection 6. Laser-mediated

2. Macro-injection 7. Silica/Carbon fibers

3. Pressure 8. Electrofusion

4. Biolistic-gene gun 9.. Electroporation

5. Protoplast 10. Particle bombardment

CHEMICAL METHODS

S.No.

1. Polyethene glycol, 4.

2. Liposome-mediated transfer 5. Artificial lipid

3. Dendrimers 6. Calcium phosphate

BIOLOGICAL METHODS

S.No.

1. Agrobacterium-mediated

2. Virus-mediated

6,7,16,8–15

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Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

ELECTROPORATION

Electroporation is a physical phenomenon in which tiny pores are formed in the cell membrane by applying a sufficiently high electric field. (Bennett et al. 2014; Delalande et al. 2015) These pores are enough for the transport for a broad range of molecules such as DNA into and out of the cell. It is a reversible and irreversible method. This occurs in the lipid bilayer of the membrane of all prokaryotes and eukaryotic cells. This method is first reported for excitable cells in 1958 and no excitable cells in 1967, for planer lipid bilayers in 1979, and for lipid vesicles in 1981. 6,19 The preparation of soymilk (when soybean washed and soaked overnight and blended with water) is an example of electroporation in which cell culture exposed to an electric field. 20

MICROINJECTION

Microinjection is a physical cell transfer method in which foreign genetic material (gene of interest) directly inject into cell parts. 5,21–23 Nowadays, we developed an automated micropipette based quantitative microinjection technology. By this technology precise amount of material delivered into the cell. 24 Other several microinjection systems are also introduced which based on robotic technology to enable automated injection which high transfection efficiency. 20,25,26

AGROBACTERIUM-MEDIATED TRANSFORMATION

It is a biological method of transfer the gene of interest into the plant genome. Agrobacterium tumefaciens is gram negative soil bacteria which cause disease in the plant (many woody and some herbaceous plant) called “Crown gall disease” through its Ti plasmid which causes plant tumor. A complex process is involved in the integration of T-DNA (Ti plasmid). 8,27–30By replacing the Ti plasmid which causes infection we can solve the problem of the tumor in the plant. The 1st transgenic cotton has obtained by this method. 31,32

WHY GM FOOD NEEDED?

The word GM food is used for such crops which are formed by genetic engineering. Such plants have been altered in the laboratory to improving many interesting characteristics such as, disease resistance or to improve nutritional value. Genetic engineering helps to produce such plant with exact desire trait rapidly. (Verma 2011) For example by this technique, extract a gene which contains drought tolerance trait and inserts that gene into the different plants. The new plant will be genetically modified drought tolerance. By increasing the population food demand also increases 33. So with the help of GM food, we can increase the quantity of food by using short land but high productivity is cultivated.34 As the food was deficient many essential nutrients, (vitamins and minerals) for example, deficiency of Vitamin A causing many diseases such as (liver disorders, eye disorders)? Not only we can transfer the gene from plant to plant but we can transfer the gene from non-plant to the plants. The best example is B.t. cotton in which we take the gene from bacterial species, Bacillus thuringiensis and transfer it into the plants such as corn, cotton, etc.35

SOME GENETICALLY MODIFIED FOOD CROPS

Soybeans, Maize, Sugarcane, Canola, Cotton, Corn, Brinjal, Rice, Banana, Potato, Tomato36,37

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Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

SOME GENETICALLY MODIFIED FOOD ANIMALS

Sheep, Goats, Mice, Cow, Fish35

ADVANTAGES OF GM ORGANISMS

1. PEST RESISTANCE

Farmer uses chemical in a lot of amounts which causes much fetal disease. The consumer never likes to eat such dangerous food which shows health hazard results. Excessive use of these pesticides and fertilizers causes water toxicity. By genetic engineering, GM foods grow such as B.t. (Bacillus thuringiensis) corn can help to eliminate the application of chemical pesticides. 3,38 It’s naturally occurring bacteria which cause the death of the insect larvae by producing certain types of proteins. The gene of this protein has been transferred into crops which becomes pest resistance. 39,40

2. HERBICIDE TOLERANCE

Crop plants are genetically engendered to the herbicides which are damaging and reducing the number of crops. For example, a roundup product has been genetically modified by Monsanto. The 2010 study has found that roundup formulation causing metabolic disruption in leporinus obtusidens due to long term exposition.41 So by the production of herbicides tolerance crop, it reduces the production cost, limits the danger application of wheat killer pesticides. 42,43 Another example is maize which is genetically modified for herbicide tolerant as well as insect resistance. (Naegeli et al. 2018)

3. DISEASE RESISTANCE

There are many Microorganisms like (viruses, fungi, and bacteria) that cause plant disease. With the help of genetic engineering, we are trying to create plants that carry the gene that shows tolerance against the above microorganisms. 3,45

4. COLD RESISTANCE

Due to the cold temperature, the yield of many crops is reduced. By using the genes from cold water fish and introduce into plants such as potatoes and tobacco. By these genes, plants become cold resistance. 3,46 Barely genes are used to produce many crops cold resistance as well as all other abiotic stresses and disease resistance.47

5. VIRUS RESISTANCE

Due to the attack of the virus on crops production of the crops reduced. Therefore, genetically modified crops are produced in a different way to increase production and prevent the attack of viruses. RNA-mediated gene silencing technique is used to degrade the viral RNA and inactivated the viral DNA by methylation. 42,48 CRISPR/CAS9 technique also use to produce virus resistance crops.49,50

6. DROUGHT TOLERANCE/SALINITY TOLERANCE

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Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

By increasing the population of the world, the need for food also increases. Therefore farmers will grow more crops even in those places where the land is saline or drought. So we are trying to grow drought and saline tolerance crop plants which can withstand a long period of drought or high tolerant content in the soil. 46,51

Nowadays, GM Tomato (Solanum lycopersicum) are produced which are drought and salinity tolerance as well as confer fast growth and chilling. 52,53 By root engineering, the root size of barley is increased for the capture of essential nutrients which are important for barley. Due to this drought tolerant of barley increased.54

7. NUTRITION

Malnutrition is common in the 3rd world countries which are dependent on the single crop as rice. Only rice does not contain all types of nutritional elements (deficiency of Vitamin A). By the deficiency of the vitamin, blindness is caused which is a big problem in the 3rd world countries. If we prepare rice crop which contains additional vitamins and minerals the problem of malnutrition can be solved. Researchers at the Swiss Federal Institute for plant science have a created of GOLDEN RICE which contains a high quantity of beta-carotene (vitamin A). By this way, we can solve the problem of malnutrition in other food crops. 3 Sorghum is another staple food of many countries. Due to genetic diversity, protein contents in sorghum grain reduced. By the help of Genetic engineering, digestibility and protein content are increased. (Liu et al. 2019) Potato is another staple food of many countries. By the help of genetic engineering, many varieties developed in which nutritional components (proteins, lipids, vitamins, carbohydrates, etc.) are increased. (Bagri et al. 2018) Another many staple food crops are genetically modified.57 And in the orange, beta-carotene increased. (Pons et al. 2014)

A human requires many micro and macronutrient elements for the activity of the body. Due to the deficiency of even one nutrient, it will result in many diseases (sickness, poor health, immune deficiency in children). Some essential nutrients are in proteins (Histidine, Lysine, Valine, and Methionine) in lipids (Linoleic and Linolenic acid) in macro-elements (Na, k, Ca, Mg, S, P, and Cl) in micro-elements (Fe, Zn, Mg, As, etc.) in vitamins (A, D, E, K, C, B1, B2, B3, Niacin, etc.).Genetic engineering is used to improve all these nutrients in a crop. 8,59,60

8. PHARMACEUTICAL

Vaccines are used for the prevention of many infectious diseases. There many problems in the production of the vaccine, distribution, and delivery. To solve these entire problems, scientist produced such type of vaccine which is called edible vaccine61. Food containing health-giving additives called functional food. Researchers working to develop edible vaccines in fruits like tomato and banana. These edible vaccines are easy to administer than another injectable vaccine. 42

9. PHYTOREMEDIATION

Many heavy metals (Cu, Pb, and Zn) which are mainly produced by human activities cause the death of plants as well as essential microorganisms in the soil. 62 With the help of genetic engineering, researchers are trying to design such plants used in bioremediation (removal of contaminants by using living organisms) such as poplar trees. 63,64

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Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

DISADVANTAGES OF GENETICALLY MODIFIED ORGANISMS

The drawback of GM foods includes many environmental problems, human health problems, economical expensive, unusual taste, trade issue, antibiotic efficiency decrease and maybe cause new disease.65–68 Some other problems are the following.

1. GMOS ARE INHERENTLY UNSAFE

There are many reasons which show that the GM plants contain unique dangers. By these techniques, GM foods are prepared by alteration of genes which cause mutations. The genetic material in soybean that makes herbicide tolerant transformed into the human gut bacteria and continue the function which shows that the eating of GM crops cause foreign GM proteins to express inside our gut. 3

2. GM DIET CAUSE A CARCINOGENIC REACTION IN THE DIGESTIVE TRACT

The 1st crop submitted to FDA (food and drug administration) voluntary tomato shows evidence of . Out of 20 female rats that fed GM tomato the seven developed stomach lesion. The type of stomach lesion linked to tomatoes can lead to life-endangering hemorrhage in a person who uses aspirin to prevent blood clotting. 3

3. GM FOOD CAUSE LIVER DAMAGE

Rats that fed on GM potato had smaller and partially atrophied liver. Rats show liver lesions and other indication of toxicity when they are fed by GM corn. 69

4. GM FOOD CAUSE ANIMALS DEATH AND ORGAN DAMAGE

The mice fed with roundup ready soy had produce significantly less digestive enzymes and cancer. In rats that fed with GM potato, there, pancreases were enlarged. GM-fed animals show lesions toxicity altered enzymes production or inflammation. 370

5. GM CROPS CAUSE AN IMMUNE REACTION AND ALLERGIES

Allergic reactions produced when any foreign particle is detected and interprets with the immune system. All the GM foods according to their definition have foreign particles that are inserted into the genome. So they provoke allergic reactions when inter the body. 66,71,72 GM peas provoked and inflammatory response in mice showing that it may cause a deadly allergic reaction in the people. Scientists found that new protein in GM soybean was able to bind with IgE antibodies and provoked many dangerous allergic reactions. 73 The B.t. produced by GM crops (B.t. maize and cotton) are showing a much dangerous toxic reaction than natural verities. 74

APPLICATION OF GM FOOD IN DIFFERENT COUNTRIES

According to a survey of unites states journal, a list of different countries utilizing GM food and their percentage are given below:

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Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

1% 1%

4% 4% 6% United State Argentina Canada Brazil 21% China 63% South Africa Others

CONCLUSION

The GM food cause beneficial as well as harmful effects on the environment. But everyone somehow is using GM food in life. It is more preferred because it is using to meet the huge population of the world with healthy and nutritional food. So it has dominated its harmful impacts and it is used all over the world. It affects human beings more beneficially than its harms so we try to form more GM food to increase the desired characteristics in the food by using a gene alteration mechanism. Several laws are present which allow the safe and healthy use of GM food and limit its harmful effect on the environment.

REFERENCES

1. Dizon F, Costa S, Rock C, Harris A, Husk C, Mei J. Genetically Modified (GM) Foods and Ethical Eating. J Food Sci. 2016;81(2):R287-R291. doi:10.1111/1750-3841.13191

2. Chaudhary G, Singh SK. Biotechnology Products in Everyday Life. Springer International Publishing; 2019. doi:10.1007/978-3-319-92399-4

3. Verma C. A Review on Impacts of Genetically Modified Food on Human Health. Open Nutraceuticals J. 2011;4(1):3-11. doi:10.2174/1876396001104010003

4. Mishra S, Singh RB, Dwivedi SP, et al. Effects of nutraceuticals on genetic expressions. Open Nutraceuticals J. 2009;2:70-80. doi:10.2174/1876396000902010070

5. Zhang Y, Yu LC. Single-cell microinjection technology in cell biology. BioEssays. 2008;30(6):606-610. doi:10.1002/bies.20759

6. Kim TK, Eberwine JH. Mammalian cell transfection : the present and the future. 2010:3173-3178. doi:10.1007/s00216-010-3821-6

7. Birch RG. PLANT TRANSFORMATION: Problems and Strategies for Practical Application. Annu Rev Plant Physiol Plant Mol Biol. 1997;48(1):297-326. doi:10.1146/annurev.arplant.48.1.297

81 | P a g e ISSN (Online): 2582- 0974 Website: www.mejast.com

Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

8. Hefferon KL. Nutritionally enhanced food crops; progress and perspectives. Int J Mol Sci. 2015;16(2):3895-3914. doi:10.3390/ijms16023895

9. Naseem M, Zaman MQ, Nazih H, et al. The effects of ginkgo biloba leaf extract on metabolic disturbances associated to alloxan-induced diabetic rats. J Anim Plant Sci. 2016;26(3):627-635. doi:10.1128/MMBR.67.1.16

10. Dymek K, Rems L, Zorec B, Dejmek P, Galindo FG, Miklavčič D. Modeling electroporation of the non-treated and vacuum impregnated heterogeneous tissue of spinach leaves. Innov Food Sci Emerg Technol. 2015;29:55-64. doi:10.1016/j.ifset.2014.08.006

11. Sharei A, Zoldan J, Adamo A, et al. A vector-free microfluidic platform for intracellular delivery. Proc Natl Acad Sci. 2013;110(6):2082-2087. doi:10.1073/pnas.1218705110

12. Perrone S, Usai M, Lazzari P, Tucker SJ, Wallace HM, Zanda M. Efficient cell transfection with melamine-based gemini surfactants. Bioconjug Chem. 2013;24(2):176-187. doi:10.1021/bc3004292

13. Batista Napotnik T, Miklavčič D. In vitro electroporation detection methods – An overview. Bioelectrochemistry. 2018;120:166-182. doi:10.1016/j.bioelechem.2017.12.005

14. Kumar K, Karanwal S, Kumar Meena Chaudhary Charan Singh R, Rahul Kumar Meena Chaudhary Charan Singh C, Kumar Meena R, Jaiswal S. Role of biotechnology in crop and animal improvement for sustainable agriculture. J Pharmacogn Phytochem JPP. 2018;7(71):1120-1124. https://www.researchgate.net/profile/Kuldeep_Kumar55/publication/322959147_Role_of_biotechnology_in_crop _and_animal_improvement_for_sustainable_agriculture/links/5a79af7a45851541ce5d634b/Role-of-biotechnolog y-in-crop-and-animal-improvement-for-sustainable.

15. Saito AC, Ogura T, Fujiwara K, Murata S, Nomura SIM. Introducing micrometer-sized artificial objects into live cells: A method for cell-giant unilamellar vesicle electrofusion. PLoS One. 2014;9(9):1-8. doi:10.1371/journal.pone.0106853

16. Kumar B, Bidhan S, Krishi C, Sutradhar M, Chandra B, Viswavidyalaya K. Review Article GENETIC ENGINEERING FOR IMPARTING ABIOTIC STRESS TOLERANCE IN RICE -A REVIEW. 2016;(November).

17. Bennett WFD, Sapay N, Tieleman DP. Atomistic simulations of pore formation and closure in lipid bilayers. Biophys J. 2014;106(1):210-219. doi:10.1016/j.bpj.2013.11.4486

18. Delalande A, Leduc C, Midoux P, Postema M, Pichon C. Efficient gene delivery by sonoporation is associated with microbubble entry into cells and the clathrin-dependent endocytosis pathway. Med Biol. 2015;41(7):1913-1926. doi:10.1016/j.ultrasmedbio.2015.03.010

19. Meglic SH, Kotnik T. Electroporation-based applications in biotechnology. Handb Electroporation. 2017;3(8):2153-2169. doi:10.1007/978-3-319-32886-7_33

20. Liu X, Fernandes R, Gertsenstein M, et al. Automated microinjection of recombinant BCL-X into mouse zygotes enhances embryo development. PLoS One. 2011;6(7):1-10. doi:10.1371/journal.pone.0021687

82 | P a g e ISSN (Online): 2582- 0974 Website: www.mejast.com

Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

21. Chow YT, Chen S, Wang R, et al. Single cell transfection through precise microinjection with quantitatively controlled injection volumes. Sci Rep. 2016;6(March):1-9. doi:10.1038/srep24127

22. Ittner LM, Götz J. Pronuclear injection for the production of transgenic mice. Nat Protoc. 2007;2(5):1206-1215. doi:10.1038/nprot.2007.145

23. Ikeda SR, Lovinger DM, McCool BA, Lewis DL. Heterologous expression of metabotropic glutamate receptors in adult rat sympathetic neurons: Subtype-specific coupling to ion channels. Neuron. 1995;14(5):1029-1038. doi:10.1016/0896-6273(95)90341-0

24. Chow YT, Chen S, Liu C, et al. A high-throughput automated microinjection system for human cells with small size. IEEE/ASME Trans Mechatronics. 2016;21(2):838-850. doi:10.1109/TMECH.2015.2476362

25. Chemicals R. Potent and specific.pdf. 1998;391(February):806-811. doi:10.1038/35888

26. Sharan R, Gramm J, Yakhini Z, Ben-dor A. These authors contributed equally to this work. Relation. 2013;10(1.12):3377. doi:10.1128/MCB.00113-07

27. Earth J. Chapter 2. 2006;1902(2010):1-39. doi:10.1029/2009JB006611.2-2

28. TianZi C, ShenJie W, Jun Z, WangZhen G, TianZhen Z. Pistil drip following pollination: A simple in planta Agrobacterium-mediated transformation in cotton. Biotechnol Lett. 2010;32(4):547-555. doi:10.1007/s10529-009-0179-y

29. Hashmi JA, Zafar Y, Arshad M, Mansoor S, Asad S. Engineering cotton (Gossypium hirsutum L.) for resistance to cotton leaf curl disease using viral truncated AC1 DNA sequences. Virus Genes. 2011;42(2):286-296. doi:10.1007/s11262-011-0569-9

30. Ahmad S. Genetic Transformation of Plants: Introduction and Recent Advances. Res J Pharmacogn Phytochem. 2017;9(2):125. doi:10.5958/0975-4385.2017.00023.1

31. Firoozabady E, DeBoer DL, Merlo DJ, et al. Transformation of cotton (Gossypium hirsutum L.) by Agrobacterium tumefaciens and regeneration of transgenic plants. Plant Mol Biol. 1987;10(2):105-116. doi:10.1007/BF00016148

32. Umbeck P, Johnson G, Barton K, Swain W. Genetically Transformed Cotton (Gossypium Hirsutum L.) Plants. Bio/Technology. 1987;5(3):263-266. doi:10.1038/nm0798-822

33. Fita A, Rodríguez-Burruezo A, Boscaiu M, Prohens J, Vicente O. Breeding and Domesticating Crops Adapted to Drought and Salinity: A New Paradigm for Increasing Food Production. Front Plant Sci. 2015;6(November):1-14. doi:10.3389/fpls.2015.00978

34. Zhang C, Wohlhueter R, Zhang H. Genetically modified foods: A critical review of their promise and problems. Food Sci Hum Wellness. 2016;5(3):116-123. doi:10.1016/j.fshw.2016.04.002

35. Puhan P. Advantages and Disadvantages of Popular Genetically Modified Plants and Animals-a Review. Eur J Pharm Med Res. 2018;5(2):175-182. www.ejpmr.com.

83 | P a g e ISSN (Online): 2582- 0974 Website: www.mejast.com

Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

36. Articles R, Physician S, Program NR, Virology M, Diamond AL, Fellow D. Vitamin B-12 Associated Neurological Diseases. Contin Educ. 2006;(43):1-30. doi:10.1017/S0014479706343797

37. Xiao Y, Wu K. Recent progress on the interaction between insects and Bacillus thuringiensis crops. 2019.

38. Moellenbeck DJ, Peters ML, Bing JW, et al. Nbt0701_668.Pdf. 2001;19(July).

39. Whitman DB. Genetically Modified Foods : Harmful or Helpful ? What are genetically-modified foods ? What are some of the advantages of GM foods ? CSA Discov Guid. 2001;(April 2000):1-13. doi:10.1111/tbed.12470

40. Li FF, Wu SJ, Chen TZ, et al. Agrobacterium-mediated co-transformation of multiple genes in upland cotton. Plant Cell Tissue Organ Cult. 2009;97(3):225-235. doi:10.1007/s11240-009-9521-2

41. Barrows G, Sexton S, Zilberman D. Agricultural Biotechnology: The Promise and Prospects of Genetically Modified Crops. J Econ Perspect. 2014;28(1):99-120. doi:10.1257/jep.28.1.99

42. De Bruijn M, Verdonck-de Leeuw I, Ten Bosch L, et al. Phonetic-acoustic and feature analyses by a neural network to assess speech quality in patients treated for head and neck cancer. Proc Annu Conf Int Speech Commun Assoc INTERSPEECH. 2008:1753-1756. doi:10.1007/s10658-007-9229-2

43. Cited R. United et States Patent. 2018;2.

44. Naegeli H, Birch AN, Casacuberta J, et al. Assessment of genetically modified cotton GHB614 × T304‐40 × GHB119 for food and feed uses, import and processing under Regulation (EC) No 1829/2003 (application EFSA‐ GMO‐NL‐2014‐122). EFSA J. 2018;16(7):1-30. doi:10.2903/j.efsa.2018.5349

45. Wally O, Punja ZK. Genetic engineering for increasing fungal and bacterial disease resistance in crop plants. GM Crops. 2010;1(4):199-206. doi:10.4161/gmcr.1.4.13225

46. Wani SH, Kumar V, Shriram V, Sah SK. Phytohormones and their metabolic engineering for abiotic stress tolerance in crop plants. Crop J. 2016;4(3):162-176. doi:10.1016/j.cj.2016.01.010

47. Gürel F, Öztürk ZN, Uçarlı C, Rosellini D. Barley Genes as Tools to Confer Abiotic Stress Tolerance in Crops. Front Plant Sci. 2016;7(August). doi:10.3389/fpls.2016.01137

48. Kreuze JF, Valkonen JP. Utilization of engineered resistance to viruses in crops of the developing world, with emphasis on sub-Saharan Africa. Curr Opin Virol. 2017;26(Cmd):90-97. doi:10.1016/j.coviro.2017.07.022

49. Zaidi SS-A, Tashkandi M, Mansoor S, Mahfouz MM. Engineering Plant Immunity: Using CRISPR/Cas9 to Generate Virus Resistance. Front Plant Sci. 2016;7(November):1-10. doi:10.3389/fpls.2016.01673

50. Khatodia S, Bhatotia K, Tuteja N. Development of CRISPR / Cas9 mediated virus resistance in agriculturally important crops. 2017;5979. doi:10.1080/21655979.2017.1297347

51. Mahmood A, Amaya R, Turgay OC, Yaprak AE, Taniguchi T, Kataoka R. High salt tolerant plant growth promoting rhizobacteria from the common ice-plant Mesembryanthemum crystallinum L. Rhizosphere. 2019;9(November 2018):10-17. doi:10.1016/j.rhisph.2018.10.004

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52. Ali A, Muzaffar A, Awan MMF, Din S, Nasir IA, Husnain T. Genetically Modified Foods: Engineered tomato with extra advantages. Adv Life Sci. 2014;(JANUARY):139-152. http://www.als-journal.com/articles/vol1issue3/Genetically_modified_foods_engineered_tomato_advantages.pdf.

53. Gerszberg A, Hnatuszko-Konka K. Tomato tolerance to abiotic stress: a review of most often engineered target sequences. Plant Growth Regul. 2017;83(2):175-198. doi:10.1007/s10725-017-0251-x

54. Ramireddy E, Hosseini SA, Eggert K, et al. Root Engineering in Barley: Increasing Cytokinin Degradation Produces a Larger Root System, Mineral Enrichment in the Shoot and Improved Drought Tolerance. Plant Physiol. 2018;177(3):1078-1095. doi:10.1104/pp.18.00199

55. Liu G, Gilding EK, Kerr ED, et al. Increasing protein content and digestibility in sorghum grain with a approach. J Cereal Sci. 2019;85(November 2018):27-34. doi:10.1016/j.jcs.2018.11.001

56. Bagri DS, Upadhyay DC, Jain SK, Prakash C. Biotechnological improvement of nutritional and therapeutic value of cultivated potato 3 . PATHWAY ENGINEERING FOR ENHANCED AMINO ACID / PROTEIN. 2018;(1):217-228.

57. Garcia-Casal MN, Peña-Rosas JP, Giyose B, et al. Staple crops biofortified with increased vitamins and minerals: considerations for a public health strategy. Ann N Y Acad Sci. 2017;1390(1):3-13. doi:10.1111/nyas.13293

58. Pons E, Alquézar B, Rodríguez A, et al. Metabolic engineering of β-carotene in orange fruit increases its in vivo antioxidant properties. Plant Biotechnol J. 2014;12(1):17-27. doi:10.1111/pbi.12112

59. Welch RM, Graham RD. Breeding for micronutrients in staple food crops from a human nutrition perspective. J Exp Bot. 2004;55(396):353-364. doi:10.1093/jxb/erh064

60. Blancquaert D, De Steur H, Gellynck X, Van Der Straeten D. Metabolic engineering of micronutrients in crop plants. Ann N Y Acad Sci. 2017;1390(1):59-73. doi:10.1111/nyas.13274

doi:10.1360/zd-2013-43-6-1064 .1-11:(2);2011 .בתמרים הקוראת No Title .ר מזלי .61

62. Chauhan P, Mathur J. Potential of Helianthus annuus for phytoremediation of multiple pollutants in the environment : A Review. 2018;4:5-16.

63. Wu Z, Bañuelos GS, Lin Z-Q, et al. Biofortification and phytoremediation of selenium in China. Front Plant Sci. 2015;6(March):1-8. doi:10.3389/fpls.2015.00136

64. Oh K, Cao T, Li T, Cheng H. Study on Application of Phytoremediation Technology in Management and Remediation of Contaminated Soils. J Clean Energy Technol. 2014;(201209026):216-220. doi:10.7763/JOCET.2014.V2.126

65. Mishra S. Physiological and Biochemical Significance of Genetically Modified Foods: An Overview. Open Nutraceuticals J. 2013;6(1):18-26. doi:10.2174/1876396001306010018

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Middle East Journal of Applied Science & Technology (MEJAST)

(Peer Reviewed International Journal) Volume 2, Issue 3, Pages 75-86, July-September 2019

66. Jainuddinmull SM. An Overview of Genetically Modified Crops. J Pharmacogn Phytochem. 2018;7(1):2405-2410.

67. Mba JMS. Survey Reports Improved Health After Avoiding Genetically Modified Foods Part 2 : Survey Results Part 3 : Focus on Digestive Disorders. 2017.

68. Mathur R. Genetic Engineering and Biosafety in the use of Genetically Modified Foods. Int J Adv Sci Res Manag Spec Issue I. 2018;(I). www.ijasrm.com.

69. Smith EC, Taylor-Robinson AW. Parasite-specific immunoglobulin isotypes during lethal and non-lethal murine malaria infections. Parasitol Res. 2003;89(1):26-33. doi:10.1016/j.redox.2017.01.019

70. Daily Mail T. Cancer row over GM foods as French study claims it did THIS to rats... and can cause organ damage and early death in humans. Dly Mail. 2012:1-11. http://www.dailymail.co.uk/sciencetech/article-2205509/Cancer-row-GM-foods-French-study-claims-did-THIS-r ats--cause-organ-damage-early-death-humans.html?openGraphAuthor=%2Fhome%2Fsearch.html%3Fs%3D%26 authornamef%3DSean%2BPoulter.

71. Lozano-Ojalvo D, Berin C, Tordesillas L. Immune basis of food allergic reactions. J Investig Allergol Clin Immunol. 2018;29(1):1-34. doi:10.18176/jiaci.0355

72. Yavari B, Sarami S, Shahgaldi S, Athari SS, Sharma A. If there is really a Notable Concern about allergenicity of genetically modified foods? J Food Qual Hazards Control. 2016;3(1):3-9.

73. Remington B, Broekman HCH, Blom WM, et al. Approaches to assess IgE mediated allergy risks (sensitization and cross-reactivity) from new or modified dietary proteins. Food Chem Toxicol. 2018;112(December 2017):97-107. doi:10.1016/j.fct.2017.12.025

74. Carzoli AK, Aboobucker SI, Sandall LL, Lübberstedt TT, Suza WP. Risks and opportunities of GM crops: Bt maize example. Glob Food Sec. 2018;19(October):84-91. doi:10.1016/j.gfs.2018.10.004

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