|Part of a series on|
|History and topics|
Genetic engineering, also called genetic modification, is the direct manipulation of an organism's genome using biotechnology. New DNA may be inserted in the host genome by first isolating and copying the genetic material of interest using molecular cloning methods to generate a DNA sequence, or by synthesizing the DNA, and then inserting this construct into the host organism. Genes may be removed, or "knocked out", using a nuclease. Gene targeting is a different technique that uses homologous recombination to change an endogenous gene, and can be used to delete a gene, remove exons, add a gene, or introduce point mutations.
An organism that is generated through genetic engineering is considered to be a genetically modified organism (GMO). The first GMOs were bacteria in 1973 and GM mice were generated in 1974. Insulin-producing bacteria were commercialized in 1982 and genetically modified food has been sold since 1994. Glofish, the first GMO designed as a pet, was first sold in the United States December in 2003.
Genetic engineering techniques have been applied in numerous fields including research, agriculture, industrial biotechnology, and medicine. Enzymes used in laundry detergent and medicines such as insulin and human growth hormone are now manufactured in GM cells, experimental GM cell lines and GM animals such as mice or zebrafish are being used for research purposes, and genetically modified crops have been commercialized.
- 1 Definition
- 2 Genetically modified organisms
- 3 History
- 4 Process
- 5 Applications
- 6 Regulation
- 7 Controversy
- 8 See also
- 9 References
- 10 Further reading
- 11 External links
Genetic engineering alters the genetic make-up of an organism using techniques that remove heritable material or that introduce DNA prepared outside the organism either directly into the host or into a cell that is then fused or hybridized with the host. This involves using recombinant nucleic acid (DNA or RNA) techniques to form new combinations of heritable genetic material followed by the incorporation of that material either indirectly through a vector system or directly through micro-injection, macro-injection and micro-encapsulation techniques.
Genetic engineering does not normally include traditional animal and plant breeding, in vitro fertilisation, induction of polyploidy, mutagenesis and cell fusion techniques that do not use recombinant nucleic acids or a genetically modified organism in the process. However the European Commission has also defined genetic engineering broadly as including selective breeding and other means of artificial selection. Cloning and stem cell research, although not considered genetic engineering, are closely related and genetic engineering can be used within them. Synthetic biology is an emerging discipline that takes genetic engineering a step further by introducing artificially synthesized genetic material from raw materials into an organism.
If genetic material from another species is added to the host, the resulting organism is called transgenic. If genetic material from the same species or a species that can naturally breed with the host is used the resulting organism is called cisgenic. Genetic engineering can also be used to remove genetic material from the target organism, creating a gene knockout organism. In Europe genetic modification is synonymous with genetic engineering while within the United States of America it can also refer to conventional breeding methods. The Canadian regulatory system is based on whether a product has novel features regardless of method of origin. In other words, a product is regulated as genetically modified if it carries some trait not previously found in the species whether it was generated using traditional breeding methods (e.g., selective breeding, cell fusion, mutation breeding) or genetic engineering. Within the scientific community, the term genetic engineering is not commonly used; more specific terms such as transgenic are preferred.
Genetically modified organisms
Plants, animals or micro organisms that have changed through genetic engineering are termed genetically modified organisms or GMOs. Bacteria were the first organisms to be genetically modified. Plasmid DNA containing new genes can be inserted into the bacterial cell and the bacteria will then express those genes. These genes can code for medicines or enzymes that process food and other substrates. Plants have been modified for insect protection, herbicide resistance, virus resistance, enhanced nutrition, tolerance to environmental pressures and the production of edible vaccines. Most commercialised GMO's are insect resistant and/or herbicide tolerant crop plants. Genetically modified animals have been used for research, model animals and the production of agricultural or pharmaceutical products. They include animals with genes knocked out, increased susceptibility to disease, hormones for extra growth and the ability to express proteins in their milk.
Humans have altered the genomes of species for thousands of years through artificial selection and more recently mutagenesis. Genetic engineering as the direct manipulation of DNA by humans outside breeding and mutations has only existed since the 1970s. The term "genetic engineering" was first coined by Jack Williamson in his science fiction novel Dragon's Island, published in 1951, one year before DNA's role in heredity was confirmed by Alfred Hershey and Martha Chase, and two years before James Watson and Francis Crick showed that the DNA molecule has a double-helix structure.
In 1972 Paul Berg created the first recombinant DNA molecules by combining DNA from the monkey virus SV40 with that of the lambda virus. In 1973 Herbert Boyer and Stanley Cohen created the first transgenic organism by inserting antibiotic resistance genes into the plasmid of an E. coli bacterium. A year later Rudolf Jaenisch created a transgenic mouse by introducing foreign DNA into its embryo, making it the world’s first transgenic animal. These achievements led to concerns in the scientific community about potential risks from genetic engineering, which were first discussed in depth at the Asilomar Conference in 1975. One of the main recommendations from this meeting was that government oversight of recombinant DNA research should be established until the technology was deemed safe.
In 1976 Genentech, the first genetic engineering company, was founded by Herbert Boyer and Robert Swanson and a year later the company produced a human protein (somatostatin) in E.coli. Genentech announced the production of genetically engineered human insulin in 1978. In 1980, the U.S. Supreme Court in the Diamond v. Chakrabarty case ruled that genetically altered life could be patented. The insulin produced by bacteria, branded humulin, was approved for release by the Food and Drug Administration in 1982.
In the 1970s graduate student Steven Lindow of the University of Wisconsin–Madison with D.C. Arny and C. Upper found a bacterium he identified as P. syringae that played a role in ice nucleation and in 1977, he discovered a mutant ice-minus strain. Later, he successfully created a recombinant ice-minus strain. In 1983, a biotech company, Advanced Genetic Sciences (AGS) applied for U.S. government authorization to perform field tests with the ice-minus strain of P. syringae to protect crops from frost, but environmental groups and protestors delayed the field tests for four years with legal challenges. In 1987, the ice-minus strain of P. syringae became the first genetically modified organism (GMO) to be released into the environment when a strawberry field and a potato field in California were sprayed with it. Both test fields were attacked by activist groups the night before the tests occurred: "The world's first trial site attracted the world's first field trasher".
The first field trials of genetically engineered plants occurred in France and the USA in 1986, tobacco plants were engineered to be resistant to herbicides. The People’s Republic of China was the first country to commercialize transgenic plants, introducing a virus-resistant tobacco in 1992. In 1994 Calgene attained approval to commercially release the Flavr Savr tomato, a tomato engineered to have a longer shelf life. In 1994, the European Union approved tobacco engineered to be resistant to the herbicide bromoxynil, making it the first genetically engineered crop commercialized in Europe. In 1995, Bt Potato was approved safe by the Environmental Protection Agency, after having been approved by the FDA, making it the first pesticide producing crop to be approved in the USA. In 2009 11 transgenic crops were grown commercially in 25 countries, the largest of which by area grown were the USA, Brazil, Argentina, India, Canada, China, Paraguay and South Africa.
In 2010, scientists at the J. Craig Venter Institute, announced that they had created the first synthetic bacterial genome. The researchers added the new genome to bacterial cells and selected for cells that contained the new genome. To do this the cells undergoes a process called resolution, where during bacterial cell division one new cell receives the original DNA genome of the bacteria, whilst the other receives the new synthetic genome. When this cell replicates it uses the synthetic genome as its template. The resulting bacterium the researchers developed, named Synthia, was the world's first synthetic life form.
The first step is to choose and isolate the gene that will be inserted into the genetically modified organism. As of 2012, most commercialised GM plants have genes transferred into them that provide protection against insects or tolerance to herbicides. The gene can be isolated using restriction enzymes to cut DNA into fragments and gel electrophoresis to separate them out according to length. Polymerase chain reaction (PCR) can also be used to amplify up a gene segment, which can then be isolated through gel electrophoresis. If the chosen gene or the donor organism's genome has been well studied it may be present in a genetic library. If the DNA sequence is known, but no copies of the gene are available, it can be artificially synthesized.
The gene to be inserted into the genetically modified organism must be combined with other genetic elements in order for it to work properly. The gene can also be modified at this stage for better expression or effectiveness. As well as the gene to be inserted most constructs contain a promoter and terminator region as well as a selectable marker gene. The promoter region initiates transcription of the gene and can be used to control the location and level of gene expression, while the terminator region ends transcription. The selectable marker, which in most cases confers antibiotic resistance to the organism it is expressed in, is needed to determine which cells are transformed with the new gene. The constructs are made using recombinant DNA techniques, such as restriction digests, ligations and molecular cloning. The manipulation of the DNA generally occurs within a plasmid.
The most common form of genetic engineering involves inserting new genetic material randomly within the host genome. Other techniques allow new genetic material to be inserted at a specific location in the host genome or generate mutations at desired genomic loci capable of knocking out endogenous genes. The technique of gene targeting uses homologous recombination to target desired changes to a specific endogenous gene. This tends to occur at a relatively low frequency in plants and animals and generally requires the use of selectable markers. The frequency of gene targeting can be greatly enhanced with the use of engineered nucleases such as zinc finger nucleases, engineered homing endonucleases, or nucleases created from TAL effectors. In addition to enhancing gene targeting, engineered nucleases can also be used to introduce mutations at endogenous genes that generate a gene knockout.
Only about 1% of bacteria are naturally capable of taking up foreign DNA. However, this ability can be induced in other bacteria via stress (e.g. thermal or electric shock), thereby increasing the cell membrane's permeability to DNA; up-taken DNA can either integrate with the genome or exist as extrachromosomal DNA. DNA is generally inserted into animal cells using microinjection, where it can be injected through the cell's nuclear envelope directly into the nucleus or through the use of viral vectors. In plants the DNA is generally inserted using Agrobacterium-mediated recombination or biolistics.
In Agrobacterium-mediated recombination, the plasmid construct contains T-DNA, DNA which is responsible for insertion of the DNA into the host plants genome. This plasmid is transformed into Agrobacterium containing no plasmids prior to infecting the plant cells. The Agrobacterium will then naturally insert the genetic material into the plant cells. In biolistics transformation particles of gold or tungsten are coated with DNA and then shot into young plant cells or plant embryos. Some genetic material will enter the cells and transform them. This method can be used on plants that are not susceptible to Agrobacterium infection and also allows transformation of plant plastids. Another transformation method for plant and animal cells is electroporation. Electroporation involves subjecting the plant or animal cell to an electric shock, which can make the cell membrane permeable to plasmid DNA. In some cases the electroporated cells will incorporate the DNA into their genome. Due to the damage caused to the cells and DNA the transformation efficiency of biolistics and electroporation is lower than agrobacterial mediated transformation and microinjection.
As often only a single cell is transformed with genetic material the organism must be regenerated from that single cell. As bacteria consist of a single cell and reproduce clonally regeneration is not necessary. In plants this is accomplished through the use of tissue culture. Each plant species has different requirements for successful regeneration through tissue culture. If successful an adult plant is produced that contains the transgene in every cell. In animals it is necessary to ensure that the inserted DNA is present in the embryonic stem cells. Selectable markers are used to easily differentiate transformed from untransformed cells. These markers are usually present in the transgenic organism, although a number of strategies have been developed that can remove the selectable marker from the mature transgenic plant. When the offspring is produced they can be screened for the presence of the gene. All offspring from the first generation will be heterozygous for the inserted gene and must be mated together to produce a homozygous animal.
Further testing uses PCR, Southern hybridization, and DNA sequencing is conducted to confirm that an organism contains the new gene. These tests can also confirm the chromosomal location and copy number of the inserted gene. The presence of the gene does not guarantee it will be expressed at appropriate levels in the target tissue so methods that look for and measure the gene products (RNA and protein) are also used. These include northern hybridization, quantitative RT-PCR, Western blot, immunofluorescence, ELISA and phenotypic analysis. For stable transformation the gene should be passed to the offspring in a Mendelian inheritance pattern, so the organism's offspring are also studied.
Genome editing is a type of genetic engineering in which DNA is inserted, replaced, or removed from a genome using artificially engineered nucleases, or "molecular scissors." The nucleases create specific double-stranded break (DSBs) at desired locations in the genome, and harness the cell’s endogenous mechanisms to repair the induced break by natural processes of homologous recombination (HR) and nonhomologous end-joining (NHEJ). There are currently four families of engineered nucleases: meganucleases, zinc finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and CRISPRs.
Genetic engineering has applications in medicine, research, industry and agriculture and can be used on a wide range of plants, animals and micro organisms.
In medicine, genetic engineering has been used to mass-produce insulin, human growth hormones, follistim (for treating infertility), human albumin, monoclonal antibodies, antihemophilic factors, vaccines and many other drugs. Vaccination generally involves injecting weak, live, killed or inactivated forms of viruses or their toxins into the person being immunized. Genetically engineered viruses are being developed that can still confer immunity, but lack the infectious sequences. Mouse hybridomas, cells fused together to create monoclonal antibodies, have been humanised through genetic engineering to create human monoclonal antibodies. Genetic engineering has shown promise for treating certain forms of cancer.
Genetic engineering is used to create animal models of human diseases. Genetically modified mice are the most common genetically engineered animal model. They have been used to study and model cancer (the oncomouse), obesity, heart disease, diabetes, arthritis, substance abuse, anxiety, aging and Parkinson disease. Potential cures can be tested against these mouse models. Also genetically modified pigs have been bred with the aim of increasing the success of pig to human organ transplantation.
Gene therapy is the genetic engineering of humans by replacing defective human genes with functional copies. This can occur in somatic tissue or germline tissue. If the gene is inserted into the germline tissue it can be passed down to that person's descendants. Gene therapy has been successfully used to treat multiple diseases, including X-linked SCID, chronic lymphocytic leukemia (CLL), and Parkinson's disease. In 2012, Glybera became the first gene therapy treatment to be approved for clinical use in either Europe or the United States after its endorsement by the European Commission. There are also ethical concerns should the technology be used not just for treatment, but for enhancement, modification or alteration of a human beings' appearance, adaptability, intelligence, character or behavior. The distinction between cure and enhancement can also be difficult to establish. Transhumanists consider the enhancement of humans desirable.
Genetic engineering is an important tool for natural scientists. Genes and other genetic information from a wide range of organisms are transformed into bacteria for storage and modification, creating genetically modified bacteria in the process. Bacteria are cheap, easy to grow, clonal, multiply quickly, relatively easy to transform and can be stored at -80 °C almost indefinitely. Once a gene is isolated it can be stored inside the bacteria providing an unlimited supply for research.
Organisms are genetically engineered to discover the functions of certain genes. This could be the effect on the phenotype of the organism, where the gene is expressed or what other genes it interacts with. These experiments generally involve loss of function, gain of function, tracking and expression.
- Loss of function experiments, such as in a gene knockout experiment, in which an organism is engineered to lack the activity of one or more genes. A knockout experiment involves the creation and manipulation of a DNA construct in vitro, which, in a simple knockout, consists of a copy of the desired gene, which has been altered such that it is non-functional. Embryonic stem cells incorporate the altered gene, which replaces the already present functional copy. These stem cells are injected into blastocysts, which are implanted into surrogate mothers. This allows the experimenter to analyze the defects caused by this mutation and thereby determine the role of particular genes. It is used especially frequently in developmental biology. Another method, useful in organisms such as Drosophila (fruit fly), is to induce mutations in a large population and then screen the progeny for the desired mutation. A similar process can be used in both plants and prokaryotes.
- Gain of function experiments, the logical counterpart of knockouts. These are sometimes performed in conjunction with knockout experiments to more finely establish the function of the desired gene. The process is much the same as that in knockout engineering, except that the construct is designed to increase the function of the gene, usually by providing extra copies of the gene or inducing synthesis of the protein more frequently.
- Tracking experiments, which seek to gain information about the localization and interaction of the desired protein. One way to do this is to replace the wild-type gene with a 'fusion' gene, which is a juxtaposition of the wild-type gene with a reporting element such as green fluorescent protein (GFP) that will allow easy visualization of the products of the genetic modification. While this is a useful technique, the manipulation can destroy the function of the gene, creating secondary effects and possibly calling into question the results of the experiment. More sophisticated techniques are now in development that can track protein products without mitigating their function, such as the addition of small sequences that will serve as binding motifs to monoclonal antibodies.
- Expression studies aim to discover where and when specific proteins are produced. In these experiments, the DNA sequence before the DNA that codes for a protein, known as a gene's promoter, is reintroduced into an organism with the protein coding region replaced by a reporter gene such as GFP or an enzyme that catalyzes the production of a dye. Thus the time and place where a particular protein is produced can be observed. Expression studies can be taken a step further by altering the promoter to find which pieces are crucial for the proper expression of the gene and are actually bound by transcription factor proteins; this process is known as promoter bashing.
Using genetic engineering techniques one can transform microorganisms such as bacteria or yeast, or transform cells from multicellular organisms such as insects or mammals, with a gene coding for a useful protein, such as an enzyme, so that the transformed organism will overexpress the desired protein. One can manufacture mass quantities of the protein by growing the transformed organism in bioreactor equipment using techniques of industrial fermentation, and then purifying the protein. Some genes do not work well in bacteria, so yeast, insect cells, or mammalians cells, each a eukaryote, can also be used. These techniques are used to produce medicines such as insulin, human growth hormone, and vaccines, supplements such as tryptophan, aid in the production of food (chymosin in cheese making) and fuels. Other applications involving genetically engineered bacteria being investigated involve making the bacteria perform tasks outside their natural cycle, such as making biofuels, cleaning up oil spills, carbon and other toxic waste and detecting arsenic in drinking water.
Experimental, lab scale industrial applications
Bacteria have been engineered to function as sensors by expressing a fluorescent protein under certain environmental conditions.
One of the best-known and controversial applications of genetic engineering is the creation and use of genetically modified crops or genetically modified organisms, such as genetically modified fish, which are used to produce genetically modified food and materials with diverse uses. There are four main goals in generating genetically modified crops.
One goal, and the first to be realized commercially, is to provide protection from environmental threats, such as cold (in the case of Ice-minus bacteria), or pathogens, such as insects or viruses, and/or resistance to herbicides. There are also fungal and virus resistant crops developed or in development. They have been developed to make the insect and weed management of crops easier and can indirectly increase crop yield.
Another goal in generating GMOs is to modify the quality of produce by, for instance, increasing the nutritional value or providing more industrially useful qualities or quantities. The Amflora potato, for example, produces a more industrially useful blend of starches. Cows have been engineered to produce more protein in their milk to facilitate cheese production. Soybeans and canola have been genetically modified to produce more healthy oils.
Another goal consists of driving the GMO to produce materials that it does not normally make. One example is "pharming", which uses crops as bioreactors to produce vaccines, drug intermediates, or drug themselves; the useful product is purified from the harvest and then used in the standard pharmaceutical production process. Cows and goats have been engineered to express drugs and other proteins in their milk, and in 2009 the FDA approved a drug produced in goat milk.
Another goal in generating GMOs, is to directly improve yield by accelerating growth, or making the organism more hardy (for plants, by improving salt, cold or drought tolerance). Some agriculturally important animals have been genetically modified with growth hormones to increase their size.
The genetic engineering of agricultural crops can increase the growth rates and resistance to different diseases caused by pathogens and parasites. This is beneficial as it can greatly increase the production of food sources with the usage of fewer resources that would be required to host the world's growing populations. These modified crops would also reduce the usage of chemicals, such as fertilizers and pesticides, and therefore decrease the severity and frequency of the damages produced by these chemical pollution.
Ethical and safety concerns have been raised around the use of genetically modified food. A major safety concern relates to the human health implications of eating genetically modified food, in particular whether toxic or allergic reactions could occur. Gene flow into related non-transgenic crops, off target effects on beneficial organisms and the impact on biodiversity are important environmental issues. Ethical concerns involve religious issues, corporate control of the food supply, intellectual property rights and the level of labeling needed on genetically modified products.
BioArt and entertainment
The regulation of genetic engineering concerns the approaches taken by governments to assess and manage the risks associated with the development and release of genetically modified crops. There are differences in the regulation of GM crops between countries, with some of the most marked differences occurring between the USA and Europe. Regulation varies in a given country depending on the intended use of the products of the genetic engineering. For example, a crop not intended for food use is generally not reviewed by authorities responsible for food safety.
Critics have objected to use of genetic engineering per se on several grounds, including ethical concerns, ecological concerns, and economic concerns raised by the fact GM techniques and GM organisms are subject to intellectual property law. GMOs also are involved in controversies over GM food with respect to whether food produced from GM crops is safe, whether it should be labeled, and whether GM crops are needed to address the world's food needs. See the genetically modified food controversies article for discussion of issues about GM crops and GM food. These controversies have led to litigation, international trade disputes, and protests, and to restrictive regulation of commercial products in some countries.
- Biological engineering
- Gene patent
- Gene drive
- Genetic engineering in the United States
- Genetically modified crops
- Genetically modified food
- Genetically modified food controversies
- Genetically modified organisms
- Induced stem cells
- Marker assisted selection, a way to select suitable offspring without using genetic engineering
- Regulation of the release of genetic modified organisms
- "First transgenic pet, ‘GloFish’, sold to US public". PHG Foundation. January 9, 2004.
- "Terms and Acronyms".
|last1=in Authors list (help)
- Vert, Michel; Doi, Yoshiharu; Hellwich, Karl-Heinz; Hess, Michael; Hodge, Philip; Kubisa, Przemyslaw; Rinaudo, Marguerite; Schué, François (2012). "Terminology for biorelated polymers and applications (IUPAC Recommendations 2012)". Pure and Applied Chemistry 84 (2): 377–410. doi:10.1351/PAC-REC-10-12-04.
- The European Parliament and the council of the European Union (12 March 2001). "Directive on the release of genetically modified organisms (GMOs) Directive 2001/18/EC ANNEX I A". Official Journal of the European Communities. p. page 17.
- Staff Economic Impacts of Genetically Modified Crops on the Agri-Food Sector; P. 42 Glossary - Term and Definitions The European Commission Directorate-General for Agriculture, "Genetic engineering: The manipulation of an organism's genetic endowment by introducing or eliminating specific genes through modern molecular biology techniques. A broad definition of genetic engineering also includes selective breeding and other means of artificial selection.", Retrieved 5 November 2012
- Van Eenennaam, Alison. "Is Livestock Cloning Another Form of Genetic Engineering?". agbiotech.
- David M. Suter, Michel Dubois-Dauphin, Karl-Heinz Krause (2006). "Genetic engineering of embryonic stem cells". Swiss Med Wkly 136 (27–28): 413–415. PMID 16897894.
- Ernesto Andrianantoandro, Subhayu Basu, David K Kariga & Ron Weiss (16 May 2006). "Synthetic biology: new engineering rules for an emerging discipline". Molecular Systems Biology 2 (2006.0028): 2006.0028. doi:10.1038/msb4100073. PMC 1681505. PMID 16738572.
- Jacobsen, E.; Schouten, H. J. (2008). "Cisgenesis, a New Tool for Traditional Plant Breeding, Should be Exempted from the Regulation on Genetically Modified Organisms in a Step by Step Approach". Potato Research 51: 75. doi:10.1007/s11540-008-9097-y.
- Capecchi, Mario R. (2001). "Generating mice with targeted mutations". Nature Medicine 7 (10): 1086–90. doi:10.1038/nm1001-1086. PMID 11590420.
- Staff Biotechnology - Glossary of Agricultural Biotechnology Terms United States Department of Agriculture, "Genetic modification: The production of heritable improvements in plants or animals for specific uses, via either genetic engineering or other more traditional methods. Some countries other than the United States use this term to refer specifically to genetic engineering.", Retrieved 5 November 2012
- James H. Maryanski (19 October 1999). "Genetically Engineered Foods". Center for Food Safety and Applied Nutrition at the Food and Drug Administration.
- Evans, Brent and Lupescu, Mihai (15 July 2012) Canada - Agricultural Biotechnology Annual – 2012 GAIN (Global Agricultural Information Network) report CA12029, United States Department of Agriculture, Foreifn Agricultural Service, Retrieved 5 November 2012
- McHugen, Alan (September 14, 2000). "Chapter 1: Hors-d'oeuvres and entrees/What is genetic modification? What are GMOs?". Pandora's Picnic Basket. Oxford University Press. ISBN 978-0198506744.
- Staff (28 November 2005) Health Canada - The Regulation of Genetically Modified Food Glossary definition of Genetically Modified: "An organism, such as a plant, animal or bacterium, is considered genetically modified if its genetic material has been altered through any method, including conventional breeding. A 'GMO' is a genetically modified organism.", Retrieved 5 November 2012
- "What is genetic modification (GM)?". CSIRO.
- "Genetic Modification of Bacteria". Annenberg Foundation.
- Panesar, Pamit et al (2010) "Enzymes in Food Processing: Fundamentals and Potential Applications", Chapter 10, I K International Publishing House, ISBN 978-9380026336
- "GM traits list". International Service for the Acquisition of Agri-Biotech Applications.
- "ISAAA Brief 43-2011: Executive Summary". International Service for the Acquisition of Agri-Biotech Applications.
- Steve Connor (2 November 2007). "The mouse that shook the world". The Independent.
- Stableford, Brian M. (2004). Historical dictionary of science fiction literature. p. 133. ISBN 9780810849389.
- Hershey A, Chase M (1952). "Independent functions of viral protein and nucleic acid in growth of bacteriophage" (PDF). J Gen Physiol 36 (1): 39–56. doi:10.1085/jgp.36.1.39. PMC 2147348. PMID 12981234.
- Jackson, DA; Symons, RH; Berg, P (1 October 1972). "Biochemical Method for Inserting New Genetic Information into DNA of Simian Virus 40: Circular SV40 DNA Molecules Containing Lambda Phage Genes and the Galactose Operon of Escherichia coli". PNAS 69 (10): 2904–2909. Bibcode:1972PNAS...69.2904J. doi:10.1073/pnas.69.10.2904. PMC 389671. PMID 4342968.
- Arnold, Paul (2009). "History of Genetics: Genetic Engineering Timeline".
- Stanley N. Cohen and Annie C. Y. Chang (1 May 1973). "Recircularization and Autonomous Replication of a Sheared R-Factor DNA Segment in Escherichia coli Transformants — PNAS". Pnas.org. Retrieved 17 July 2010.
- Jaenisch, R. and Mintz, B. (1974 ) Simian virus 40 DNA sequences in DNA of healthy adult mice derived from preimplantation blastocysts injected with viral DNA. Proc. Natl. Acad. 71(4) 1250–1254 
- Berg P et al.; Baltimore, D; Brenner, S; Roblin, RO; Singer, MF (1975). "Summary statement of the Asilomar Conference on recombinant DNA molecules" (PDF). Proc. Natl. Acad. Sci. U.S.A 72 (6): 1981–4. Bibcode:1975PNAS...72.1981B. doi:10.1073/pnas.72.6.1981. PMC 432675. PMID 806076.
- NIH Guidelines for research involving recombinant DNA molecules
- Goeddel, David; Dennis G. Kleid; Francisco Bolivar; Herbert L. Heyneker; Daniel G. Yansura; Roberto Crea; Tadaaki Hirose; Adam Kraszewski; Keiichi Itakura; AND Arthur D. Riggs (January 1979). "Expression in Escherichia coli of chemically synthesized genes for human insulin". PNAS 76 (1): 106–110. Bibcode:1979PNAS...76..106G. doi:10.1073/pnas.76.1.106. PMC 382885. PMID 85300.
- US Supreme Court Cases from Justia & Oyez (16 June 1980). "Diamond V Chakrabarty" 447 (303). Supreme.justia.com. Retrieved 17 July 2010.
- "Artificial Genes". TIME. 15 November 1982. Retrieved 17 July 2010.
- H. Patricia Hynes. (1989) Biotechnology in agriculture: an analysis of selected technologies and policy in the United States. Reproductive and Genetic Engineering (2)1:39–49 
- Rebecca Bratspies (2007) Some Thoughts on the American Approach to Regulating Genetically Modified Organisms. Kansas Journal of Law and Public Policy 16:393 
- BBC News 14 June 2002 GM crops: A bitter harvest?
- Thomas H. Maugh II for the Los Angeles Times. June 09, 1987. Altered Bacterium Does Its Job : Frost Failed to Damage Sprayed Test Crop, Company Says
- James, Clive (1996). "Global Review of the Field Testing and Commercialization of Transgenic Plants: 1986 to 1995". The International Service for the Acquisition of Agri-biotech Applications. Retrieved 17 July 2010.
- James, Clive (1997). "Global Status of Transgenic Crops in 1997". ISAAA Briefs No. 5.: 31.
- Bruening, G.; Lyons, J.M. (2000). "The case of the FLAVR SAVR tomato". California Agriculture 54 (4): 6. doi:10.3733/ca.v054n04p6.
- MacKenzie, Debora (18 June 1994). "Transgenic tobacco is European first". New Scientist.
- Genetically Altered Potato Ok'd For Crops Lawrence Journal-World - 6 May 1995
- Global Status of Commercialized Biotech/GM Crops: 2009 ISAAA Brief 41-2009, 23 February 2010. Retrieved 10 August 2010
- WHO (1987): Principles for the Safety Assessment of Food Additives and Contaminants in Food, Environmental Health Criteria 70. World Health Organization, Geneva
- WHO (1991): Strategies for assessing the safety of foods produced by biotechnology, Report of a Joint FAO/WHO Consultation. World Health Organization, Geneva
- WHO (1993): Health aspects of marker genes in genetically modified plants, Report of a WHO Workshop. World Health Organization, Geneva
- WHO (1995): Application of the principle of substantial equivalence to the safety evaluation of foods or food components from plants derived by modern biotechnology, Report of a WHO Workshop. World Health Organization, Geneva
- Gibson, D. G.; Glass, J. I.; Lartigue, C.; Noskov, V. N.; Chuang, R.-Y.; Algire, M. A.; Benders, G. A.; Montague, M. G.; Ma, L.; Moodie, M. M.; Merryman, C.; Vashee, S.; Krishnakumar, R.; Assad-Garcia, N.; Andrews-Pfannkoch, C.; Denisova, E. A.; Young, L.; Qi, Z.-Q.; Segall-Shapiro, T. H.; Calvey, C. H.; Parmar, P. P.; Hutchison Ca, C. A.; Smith, H. O.; Venter, J. C. (2010). "Creation of a Bacterial Cell Controlled by a Chemically Synthesized Genome". Science 329 (5987): 52–6. doi:10.1126/science.1190719. PMID 20488990.
- Sample, Ian (20 May 2010). "Craig Venter creates synthetic life form". London: guardian.co.uk.
- James, Clive (2012). "Global Status of Commercilized Biotech/GM Crops:2012". ISSA Brief No. 44.
- Alberts B, Johnson A, Lewis J, et al. (2002). "8". Isolating, Cloning, and Sequencing DNA. (4th ed.). New York: Garland Science.
- R I Kaufman and B T Nixon (1996). "Use of PCR to isolate genes encoding sigma54-dependent activators from diverse bacteria". J Bacteriol 178 (13): 3967–3970. PMC 232662. PMID 8682806.
- Liang, Jing; Luo, Yunzi; Zhao, Huimin (2011). "Synthetic biology: Putting synthesis into biology". Wiley Interdisciplinary Reviews: Systems Biology and Medicine 3: 7. doi:10.1002/wsbm.104.
- Berg, P.; Mertz, J. E. (2010). "Personal Reflections on the Origins and Emergence of Recombinant DNA Technology". Genetics 184 (1): 9–17. doi:10.1534/genetics.109.112144. PMC 2815933. PMID 20061565.
- Townsend JA, Wright DA, Winfrey RJ, et al. (May 2009). "High-frequency modification of plant genes using engineered zinc-finger nucleases". Nature 459 (7245): 442–5. Bibcode:2009Natur.459..442T. doi:10.1038/nature07845. PMC 2743854. PMID 19404258.
- Shukla VK, Doyon Y, Miller JC, et al. (May 2009). "Precise genome modification in the crop species Zea mays using zinc-finger nucleases". Nature 459 (7245): 437–41. Bibcode:2009Natur.459..437S. doi:10.1038/nature07992. PMID 19404259.
- Grizot S, Smith J, Daboussi F, et al. (September 2009). "Efficient targeting of a SCID gene by an engineered single-chain homing endonuclease". Nucleic Acids Res. 37 (16): 5405–19. doi:10.1093/nar/gkp548. PMC 2760784. PMID 19584299.
- Gao H, Smith J, Yang M, et al. (January 2010). "Heritable targeted mutagenesis in maize using a designed endonuclease". Plant J. 61 (1): 176–87. doi:10.1111/j.1365-313X.2009.04041.x. PMID 19811621.
- Christian M, Cermak T, Doyle EL, et al. (July 2010). "TAL Effector Nucleases Create Targeted DNA Double-strand Breaks". Genetics 186 (2): 757–61. doi:10.1534/genetics.110.120717. PMC 2942870. PMID 20660643.
- Li T, Huang S, Jiang WZ, et al. (August 2010). "TAL nucleases (TALNs): hybrid proteins composed of TAL effectors and FokI DNA-cleavage domain". Nucleic Acids Res 39 (1): 359–72. doi:10.1093/nar/gkq704. PMC 3017587. PMID 20699274.
- S.C. Ekker (2008). "Zinc finger-based knockout punches for zebrafish genes". Zebrafish 5 (2): 1121–3. doi:10.1089/zeb.2008.9988. PMC 2849655. PMID 18554175.
- Geurts AM, Cost GJ, Freyvert Y, et al. (July 2009). "Knockout rats via embryo microinjection of zinc-finger nucleases". Science 325 (5939): 433. Bibcode:2009Sci...325..433G. doi:10.1126/science.1172447. PMC 2831805. PMID 19628861.
- Chen I, Dubnau D (2004). "DNA uptake during bacterial transformation". Nat. Rev. Microbiol. 2 (3): 241–9. doi:10.1038/nrmicro844. PMID 15083159.
- Graham Head; Hull, Roger H; Tzotzos, George T. (2009). Genetically Modified Plants: Assessing Safety and Managing Risk. London: Academic Pr. p. 244. ISBN 0-12-374106-8.
- Gelvin, S. B. (2003). "Agrobacterium-Mediated Plant Transformation: The Biology behind the "Gene-Jockeying" Tool". Microbiology and Molecular Biology Reviews 67 (1): 16–37, table of contents. doi:10.1128/MMBR.67.1.16-37.2003. PMC 150518. PMID 12626681.
- Behrooz Darbani, Safar Farajnia, Mahmoud Toorchi, Saeed Zakerbostanabad, Shahin Noeparvar and C. Neal Stewart Jr. (2010). "DNA-Delivery Methods to Produce Transgenic Plants". Science Alert.
- Hohn, Barbara; Levy, Avraham A; Puchta, Holger (2001). "Elimination of selection markers from transgenic plants". Current Opinion in Biotechnology 12 (2): 139–43. doi:10.1016/S0958-1669(00)00188-9. PMID 11287227.
- Esvelt, KM.; Wang, HH. (2013). "Genome-scale engineering for systems and synthetic biology". Mol Syst Biol 9: 641. doi:10.1038/msb.2012.66. PMC 3564264. PMID 23340847.
- Tan, WS.; Carlson, DF.; Walton, MW.; Fahrenkrug, SC.; Hackett, PB. (2012). "Precision editing of large animal genomes". Adv Genet. Advances in Genetics 80: 37–97. doi:10.1016/B978-0-12-404742-6.00002-8. ISBN 9780124047426. PMC 3683964. PMID 23084873.
- John C. Avise (2004). The hope, hype & reality of genetic engineering: remarkable stories from agriculture, industry, medicine, and the environment. Oxford University Press US. p. 22. ISBN 978-0-19-516950-8.
- (10 December 2012) Engineering algae to make complex anti-cancer 'designer' drug PhysOrg, Retrieved 15 April 2013
- National Institute of Allergies and Infectious Diseases. "Vaccine Types". national Institute of Health.
- Rodriguez, Luis L.; Grubman, Marvin J. (2009). "Foot and mouth disease virus vaccines". Vaccine 27: D90–4. doi:10.1016/j.vaccine.2009.08.039. PMID 19837296.
- Roque AC, Lowe CR, Taipa MA. (2004). "Antibodies and genetically engineered related molecules: production and purification". Biotechnol Proress 20 (3): 639–54. doi:10.1021/bp030070k. PMID 15176864.
- Coghlan, Andy (26 March 2013) Gene therapy cures leukaemia in eight days The New Scientist, Retrieved 15 April 2013
- Coghlan, Andy (10 February 2013) Liver cancer survival time tripled by virus New Scientist, Retrieved 15 April 2013
- "Background: Cloned and Genetically Modified Animals". Center for Genetics and Society. 14 April 2005.
- "Knockout Mice". Nation Human Genome Research Institute. 2009.
- "GM pigs best bet for organ transplant". Medical News Today. 21 September 2003.
- "What is Genetic Engineering? A simple introduction". Physicians and scientists for responsible application of science and technology.
- "Gene Therapy". Oak Ridge national laboratory. 11 June 2009. Retrieved 9/7/2010. Check date values in:
- Fischer, Alain; Hacein-Bey-Abina, Salima; Cavazzana-Calvo, Marina (2010). "20 years of gene therapy for SCID". Nature Immunology 11 (6): 457–60. doi:10.1038/ni0610-457. PMID 20485269.
- Ledford, Heidi (2011). "Cell therapy fights leukaemia". Nature. doi:10.1038/news.2011.472.
- Lewitt, Peter A; Rezai, Ali R; Leehey, Maureen A; Ojemann, Steven G; Flaherty, Alice W; Eskandar, Emad N; Kostyk, Sandra K; Thomas, Karen; Sarkar, Atom; Siddiqui, Mustafa S; Tatter, Stephen B; Schwalb, Jason M; Poston, Kathleen L; Henderson, Jaimie M; Kurlan, Roger M; Richard, Irene H; Van Meter, Lori; Sapan, Christine V; During, Matthew J; Kaplitt, Michael G; Feigin, Andrew (2011). "AAV2-GAD gene therapy for advanced Parkinson's disease: A double-blind, sham-surgery controlled, randomised trial". The Lancet Neurology 10 (4): 309–19. doi:10.1016/S1474-4422(11)70039-4. PMID 21419704.
- Gallagher, James. (2 November 2012) BBC News – Gene therapy: Glybera approved by European Commission. Bbc.co.uk. Retrieved on 15 December 2012.
- Richards, Sabrina. "Gene Therapy Arrives in Europe". The Scientist. Retrieved 16 November 2012.
- Emilie R. Bergeson (1997). "The Ethics of Gene Therapy".
- Kathi E. Hanna. "Genetic Enhancement". National Human Genome Research Institute.
- "Applications of Genetic Engineering". Microbiologyprocedure. Retrieved 9/7/2010. Check date values in:
- "Biotech: What are transgenic organisms?". Easyscience. 2002. Retrieved 9/7/2010. Check date values in:
- Savage, Neil (1 August 2007). "Making Gasoline from Bacteria: A biotech startup wants to coax fuels from engineered microbes". Technology Review. Retrieved 9/7/2010. Check date values in:
- Summers, Rebecca (24 April 2013) Bacteria churn out first ever petrol-like biofuel New Scientist, Retrieved 27 April 2013
- "Application of Some Genetically Engineered Bacteria". Retrieved 9/7/2010. Check date values in:
- Sanderson, Katherine (24 February 2012) New Portable Kit Detects Arsenic In Wells Chemical and Engineering News, Retrieved 23 January 2013
- "New virus-built battery could power cars, electronic devices". Web.mit.edu. 2 April 2009. Retrieved 17 July 2010.
- "Hidden Ingredient In New, Greener Battery: A Virus". Npr.org. Retrieved 17 July 2010.
- "Researchers Synchronize Blinking 'Genetic Clocks' -- Genetically Engineered Bacteria That Keep Track of Time". ScienceDaily. 24 January 2010.
- Suszkiw, Jan (November 1999). "Tifton, Georgia: A Peanut Pest Showdown". Agricultural Research magazine. Retrieved 23 November 2008.
- Magaña-Gómez JA, de la Barca AM (2009). "Risk assessment of genetically modified crops for nutrition and health". Nutr. Rev. 67 (1): 1–16. doi:10.1111/j.1753-4887.2008.00130.x. PMID 19146501.
- Islam, Aparna (2008). "Fungus Resistant Transgenic Plants: Strategies, Progress and Lessons Learnt". Plant Tissue Culture and Biotechnology 16 (2): 117–38. doi:10.3329/ptcb.v16i2.1113.
- "Disease resistant crops". GMO Compass.
- Demont, M; Tollens, E (2004). "First impact of biotechnology in the EU: Bt maize adoption in Spain". Annals of Applied Biology 145 (2): 197–207. doi:10.1111/j.1744-7348.2004.tb00376.x.
- Deborah B. Whitman (2000). "Genetically Modified Foods: Harmful or Helpful?".
- Emma Young (2003). "GM cows to please cheese-makers". New Scientist.
- Rapeseed (canola) has been genetically engineered to modify its oil content with a gene encoding a "12:0 thioesterase" (TE) enzyme from the California bay plant (Umbellularia californica) to increase medium length fatty acids, see: Geo-pie.cornell.edu
- Bomgardner Melody M (2012). "Replacing Trans Fat: New crops from Dow Chemical and DuPont target food makers looking for stable, heart-healthy oils". Chemical and Engineering News 90 (11): 30–32.
- Marvier, Michelle (2008). "Pharmaceutical crops in California, benefits and risks. A review". Agronomy for Sustainable Development 28 (1): 1–9. doi:10.1051/agro:2007050.
- "FDA Approves First Human Biologic Produced by GE Animals". US Food and Drug Administration.
- Paulo Rebêlo (15 July 2004). "GM cow milk 'could provide treatment for blood disease'". SciDev.
- "Giant GM salmon on the way". BBC News. 11 April 2000.
- Eric Chivian, Aaron Bernstein (2008). Sustaining Life. Oxford University Press, Inc. ISBN 978-0-19-517509-7.
- Carrington, Damien (13 June 2012) GM crops good for environment, study finds The Guardian. Retrieved 16 June 2012
- John Pickrell (4 September 2006). "Introduction: GM Organisms". New Scientist.
- "20 questions on genetically modified foods". World Health Organization. 2010.
- "Can GM crops harm the environment?". National Environment Research Council (NERC).
- Jessica M. Pasko (3/4/2007). "Bio-artists bridge gap between arts, sciences: Use of living organisms is attracting attention and controversy". msnbc. Check date values in:
- Joab Jackson (6 December 2005). "Genetically Modified Bacteria Produce Living Photographs". National Geographic News.
- Phys.Org website. April 4, 2005 Plant gene replacement results in the world's only blue rose
- Katsumoto, Yukihisa; Fukuchi-Mizutani, Masako; Fukui, Yuko; Brugliera, Filippa; Holton, Timothy A.; Karan, Mirko; Nakamura, Noriko; Yonekura-Sakakibara, Keiko; Togami, Junichi; Pigeaire, Alix; Tao, Guo-Qing; Nehra, Narender S.; Lu, Chin-Yi; Dyson, Barry K.; Tsuda, Shinzo; Ashikari, Toshihiko; Kusumi, Takaaki; Mason, John G.; Tanaka, Yoshikazu (2007). "Engineering of the Rose Flavonoid Biosynthetic Pathway Successfully Generated Blue-Hued Flowers Accumulating Delphinidin". Plant and Cell Physiology 48 (11): 1589–600. doi:10.1093/pcp/pcm131. PMID 17925311.
- Published PCT Application WO2000049150 "Chimeric Gene Constructs for Generation of Fluorescent Transgenic Ornamental Fish." National University of Singapore 
- Stewart, C. Neal (2006). "Go with the glow: Fluorescent proteins to light transgenic organisms". Trends in Biotechnology 24 (4): 155–62. doi:10.1016/j.tibtech.2006.02.002. PMID 16488034.
- British Medical Association (1999). The Impact of Genetic Modification on Agriculture, Food and Health. BMJ Books. ISBN 0-7279-1431-6.
- Donnellan, Craig (2004). Genetic Modification (Issues). Independence Educational Publishers. ISBN 1-86168-288-3.
- Morgan, Sally (2003). Superfoods: Genetic Modification of Foods (Science at the Edge). Heinemann. ISBN 1-4034-4123-5.
- Smiley, Sophie (2005). Genetic Modification: Study Guide (Exploring the Issues). Independence Educational Publishers. ISBN 1-86168-307-3.
- Watson, James D. (2007). Recombinant DNA: Genes and Genomes: A Short Course. San Francisco: W.H. Freeman. ISBN 0-7167-2866-4.
- Weaver, Sean; Morris, Michael (2003). "An Annotated Bibliography of Scientific Publications on the Risks Associated with Genetic Modification". Wellington, N.Z.: Victoria University
- Zaid, A; H.G. Hughes, E. Porceddu, F. Nicholas (2001). Glossary of Biotechnology for Food and Agriculture - A Revised and Augmented Edition of the Glossary of Biotechnology and Genetic Engineering. Available in English, French, Spanish, Arabic. Rome, Italy: FAO. ISBN 92-5-104683-2.
|Library resources about
|Wikimedia Commons has media related to Genetic engineering.|
|At Wikiversity, you can learn more and teach others about Genetic engineering at the Department of Genetic engineering|
- GMO Safety - Information about research projects on the biological safety of genetically modified plants.
- GMO-compass, news on GMO en EU