Editing Genetically modified organism (section)

== Viruses ==
{{Main|Genetically modified virus}}
Viruses are often modified so they can be used as [[Viral vector|vectors]] for inserting genetic information into other organisms. This process is called [[Transduction (genetics)|transduction]] and if successful the recipient of the introduced DNA becomes a GMO. Different viruses have different efficiencies and capabilities. Researchers can use this to control for various factors; including the target location, insert size, and duration of gene expression. Any dangerous sequences inherent in the virus must be removed, while those that allow the gene to be delivered effectively are retained.<ref>{{cite journal | vauthors = Baldo A, van den Akker E, Bergmans HE, Lim F, Pauwels K | title = General considerations on the biosafety of virus-derived vectors used in gene therapy and vaccination | journal = Current Gene Therapy | volume = 13 | issue = 6 | pages = 385–94 | date = December 2013 | pmid = 24195604 | pmc = 3905712 | doi = 10.2174/15665232113136660005 }}</ref>

While viral vectors can be used to insert DNA into almost any organism it is especially relevant for its potential in treating human disease. Although primarily still at trial stages,<ref>{{cite web|url=https://ghr.nlm.nih.gov/primer/therapy/availability|title=Is gene therapy available to treat my disorder? |work = Genetics Home Reference |access-date=14 December 2018}}</ref> there has been some successes using [[gene therapy]] to replace defective genes. This is most evident in curing patients with [[severe combined immunodeficiency]] rising from [[adenosine deaminase deficiency]] (ADA-SCID),<ref name="ReferenceA">{{cite journal | vauthors = Aiuti A, Roncarolo MG, Naldini L | title = ex vivo gene therapy in Europe: paving the road for the next generation of advanced therapy medicinal products | journal = EMBO Molecular Medicine | volume = 9 | issue = 6 | pages = 737–740 | date = June 2017 | pmid = 28396566 | pmc = 5452047 | doi = 10.15252/emmm.201707573 }}</ref> although the development of [[leukemia]] in some ADA-SCID patients<ref name="Lundstrom_2018">{{cite journal | vauthors = Lundstrom K | title = Viral Vectors in Gene Therapy | journal = Diseases | volume = 6 | issue = 2 | date = May 2018 | pmid = 29883422 | pmc = 6023384 | doi = 10.3390/diseases6020042 | page=42 | doi-access = free }}</ref> along with the death of [[Jesse Gelsinger]] in a 1999 trial set back the development of this approach for many years.<ref name="Sheridan_2011">{{cite journal | vauthors = Sheridan C | title = Gene therapy finds its niche | journal = Nature Biotechnology | volume = 29 | issue = 2 | pages = 121–8 | date = February 2011 | pmid = 21301435 | doi = 10.1038/nbt.1769 | s2cid = 5063701 }}</ref> In 2009, another breakthrough was achieved when an eight-year-old boy with [[Leber's congenital amaurosis]] regained normal eyesight<ref name="Sheridan_2011" /> and in 2016 [[GlaxoSmithKline]] gained approval to commercialize a gene therapy treatment for ADA-SCID.<ref name="ReferenceA" /> As of 2018, there are a substantial number of [[clinical trial]]s underway, including treatments for [[Haemophilia|hemophilia]], [[glioblastoma]], [[chronic granulomatous disease]], [[cystic fibrosis]] and various [[cancer]]s.<ref name="Lundstrom_2018" />

The most common virus used for gene delivery comes from [[adenoviruses]] as they can carry up to 7.5 kb of foreign DNA and infect a relatively broad range of host cells, although they have been known to elicit immune responses in the host and only provide short term expression. Other common vectors are [[adeno-associated virus]]es, which have lower toxicity and longer-term expression, but can only carry about 4kb of DNA.<ref name="Lundstrom_2018" /> [[Herpes simplex virus]]es make promising vectors, having a carrying capacity of over 30kb and providing long term expression, although they are less efficient at gene delivery than other vectors.<ref>{{cite book |url= https://www.ncbi.nlm.nih.gov/books/NBK7024/ |title=HSV as a Vector in Vaccine Development and Gene Therapy | vauthors = Manservigi R, Epstein AL, Argnani R, Marconi P |date=2013 |publisher=Landes Bioscience }}</ref> The best vectors for long term integration of the gene into the host genome are [[retrovirus]]es, but their propensity for random integration is problematic. [[Lentivirus]]es are a part of the same family as retroviruses with the advantage of infecting both dividing and non-dividing cells, whereas retroviruses only target dividing cells. Other viruses that have been used as vectors include [[alphavirus]]es, [[flavivirus]]es, [[measles virus]]es, [[rhabdovirus]]es, [[Newcastle disease virus]], [[poxviruses]], and [[picornavirus]]es.<ref name="Lundstrom_2018" />

Most [[vaccine]]s consist of viruses that have been [[Attenuated vaccine|attenuated]], disabled, weakened or killed in some way so that their [[Virulence|virulent]] properties are no longer effective. Genetic engineering could theoretically be used to create viruses with the virulent genes removed. This does not affect the viruses [[infectivity]], invokes a natural immune response and there is no chance that they will regain their virulence function, which can occur with some other vaccines. As such they are generally considered safer and more efficient than conventional vaccines, although concerns remain over non-target infection, potential side effects and [[horizontal gene transfer]] to other viruses.<ref>{{cite journal | vauthors = Chan VS | title = Use of genetically modified viruses and genetically engineered virus-vector vaccines: environmental effects | journal = Journal of Toxicology and Environmental Health. Part A | volume = 69 | issue = 21 | pages = 1971–7 | date = November 2006 | pmid = 16982535 | doi = 10.1080/15287390600751405 | bibcode = 2006JTEHA..69.1971C | s2cid = 41198650 }}</ref> Another potential approach is to use vectors to create novel vaccines for diseases that have no vaccines available or the vaccines that do not work effectively, such as [[HIV/AIDS|AIDS]], [[malaria]], and [[tuberculosis]].<ref name=":21" /> The most effective vaccine against Tuberculosis, the [[BCG vaccine|Bacillus Calmette–Guérin (BCG) vaccine]], only provides partial protection. A modified vaccine expressing ''a M tuberculosis'' antigen is able to enhance BCG protection.<ref>{{cite journal | vauthors = Tameris MD, Hatherill M, Landry BS, Scriba TJ, Snowden MA, Lockhart S, Shea JE, McClain JB, Hussey GD, Hanekom WA, Mahomed H, McShane H | title = Safety and efficacy of MVA85A, a new tuberculosis vaccine, in infants previously vaccinated with BCG: a randomized, placebo-controlled phase 2b trial | journal = Lancet | volume = 381 | issue = 9871 | pages = 1021–8 | date = March 2013 | pmid = 23391465 | pmc = 5424647 | doi = 10.1016/S0140-6736(13)60177-4 }}</ref> It has been shown to be safe to use at [[phase II trials]], although not as effective as initially hoped.<ref>{{cite journal | vauthors = Delany I, Rappuoli R, De Gregorio E | title = Vaccines for the 21st century | journal = EMBO Molecular Medicine | volume = 6 | issue = 6 | pages = 708–20 | date = June 2014 | pmid = 24803000 | pmc = 4203350 | doi = 10.1002/emmm.201403876 }}</ref> Other vector-based vaccines have already been approved and many more are being developed.<ref name=":21">{{cite journal | vauthors = Ramezanpour B, Haan I, Osterhaus A, Claassen E | title = Vector-based genetically modified vaccines: Exploiting Jenner's legacy | journal = Vaccine | volume = 34 | issue = 50 | pages = 6436–6448 | date = December 2016 | pmid = 28029542 | doi = 10.1016/j.vaccine.2016.06.059 | pmc = 7115478 | doi-access = free }}</ref>

Another potential use of genetically modified viruses is to alter them so they can directly treat diseases. This can be through expression of protective proteins or by directly targeting infected cells. In 2004, researchers reported that a genetically modified virus that exploits the selfish behavior of cancer cells might offer an alternative way of killing tumours.<ref>{{Cite web|url=https://www.newscientist.com/article/dn5056-genetically-modified-virus-explodes-cancer-cells/|title=Genetically-modified virus explodes cancer cells | vauthors = Bhattacharya S |website=New Scientist}}</ref><ref>{{Cite web|url=https://www.newscientist.com/article/dn12839-gm-virus-shrinks-cancer-tumours-in-humans/|title=GM virus shrinks cancer tumours in humans | vauthors = Khamsi R |website=New Scientist}}</ref> Since then, several researchers have developed genetically modified [[oncolytic virus]]es that show promise as treatments for various types of [[cancer]].<ref>{{cite journal | vauthors = Leja J, Yu D, Nilsson B, Gedda L, Zieba A, Hakkarainen T, Åkerström G, Öberg K, Giandomenico V, Essand M | title = Oncolytic adenovirus modified with somatostatin motifs for selective infection of neuroendocrine tumor cells | journal = Gene Therapy | volume = 18 | issue = 11 | pages = 1052–62 | date = November 2011 | pmid = 21490682 | doi = 10.1038/gt.2011.54 | s2cid = 22520171 | doi-access =  }}</ref><ref>Perett, Linda (30 June 2011) [http://benchmarks.cancer.gov/2011/06/measles-viruses-genetically-modified-to-treat-ovarian-cancer/ Measles viruses genetically modified to treat ovarian cancer] National Cancer Institute, Benchmarks, Retrieved 5 September 2012</ref><ref>{{cite journal | vauthors = Breitbach CJ, Thorne SH, Bell JC, Kirn DH | title = Targeted and armed oncolytic poxviruses for cancer: the lead example of JX-594 | journal = Current Pharmaceutical Biotechnology | volume = 13 | issue = 9 | pages = 1768–72 | date = July 2012 | pmid = 21740365 | doi = 10.2174/138920112800958922 }}</ref><ref>Beasley, Deena (31 August 2011) [https://www.reuters.com/article/us-cancer-virus-idUSTRE77U4NC20110831 Cancer-fighting virus shown to target tumors alone] Reuters Science, Retrieved 5 September 2012</ref><ref name="pmid16507823">{{cite journal | vauthors = Garber K | title = China approves world's first oncolytic virus therapy for cancer treatment | journal = Journal of the National Cancer Institute | volume = 98 | issue = 5 | pages = 298–300 | date = March 2006 | pmid = 16507823 | doi = 10.1093/jnci/djj111 | doi-access = free }}</ref> In 2017, researchers genetically modified a virus to express spinach [[defensin]] proteins. The virus was injected into orange trees to combat [[citrus greening disease]] that had reduced orange production by 70% since 2005.<ref>{{cite magazine |url= https://www.wired.com/2017/04/save-floridas-famous-oranges-scientists-race-weaponize-virus/ |title=Florida's Orange Trees Are Dying, But a Weaponized Virus Could Save Them | vauthors = Molteni M |date=12 April 2017|magazine=Wired|access-date=17 April 2017}}</ref>

Natural viral diseases, such as [[myxomatosis]] and [[rabbit hemorrhagic disease]], have been used to help control pest populations. Over time the surviving pests become resistant, leading researchers to look at alternative methods. Genetically modified viruses that make the target animals infertile through [[immunocontraception]] have been created in the laboratory<ref name=":7">{{cite news|url=https://www.telegraph.co.uk/news/worldnews/australiaandthepacific/australia/1403897/GM-virus-curbs-rabbits.html|title=GM virus curbs rabbits| vauthors = Jelley J |date=7 August 2002|access-date=16 December 2018|name-list-style=vanc}}</ref> as well as others that target the developmental stage of the animal.<ref>{{cite news|url=https://www.theguardian.com/world/2005/feb/26/australia.bernardoriordan|title=Virus planned to counter cane toad| vauthors = O'Riordan B |date=26 February 2005|work=The Guardian|access-date=16 December 2018|issn=0261-3077|name-list-style=vanc}}</ref> There are concerns with using this approach regarding virus containment<ref name=":7" /> and cross species infection.<ref>{{cite web|url=https://www.newscientist.com/article/dn2647-virus-could-sterilise-australias-rabbits/|title=Virus could sterilise Australia's rabbits| vauthors = Mildura GO |website=New Scientist|access-date=16 December 2018|name-list-style=vanc}}</ref> Sometimes the same virus can be modified for contrasting purposes. Genetic modification of the [[myxoma virus]] has been proposed to conserve [[European rabbit|European wild rabbits]] in the [[Iberian Peninsula|Iberian peninsula]] and to help regulate them in Australia. To protect the Iberian species from viral diseases, the myxoma virus was genetically modified to immunize the rabbits, while in Australia the same myxoma virus was genetically modified to lower fertility in the Australian rabbit population.<ref name=":1">{{cite journal|vauthors=Angulo E, Cooke B|date=December 2002|title=First synthesize new viruses then regulate their release? The case of the wild rabbit|journal=Molecular Ecology|volume=11|issue=12|pages=2703–9|doi=10.1046/j.1365-294X.2002.01635.x|pmid=12453252|bibcode=2002MolEc..11.2703A |hdl=10261/45541|s2cid=23916432 |hdl-access=free}}</ref>

Outside of biology scientists have used a genetically modified virus to construct a [[lithium-ion battery]] and other [[nanostructure]]d materials. It is possible to engineer [[bacteriophage]]s to express modified proteins on their surface and join them up in specific patterns (a technique called [[phage display]]). These structures have potential uses for energy storage and generation, [[biosensing]] and tissue regeneration with some new materials currently produced including [[quantum dot]]s, [[liquid crystal]]s, [[nanoring]]s and [[Nanofiber|nanofibres]].<ref>{{cite journal | vauthors = Pires DP, Cleto S, Sillankorva S, Azeredo J, Lu TK | title = Genetically Engineered Phages: a Review of Advances over the Last Decade | journal = Microbiology and Molecular Biology Reviews | volume = 80 | issue = 3 | pages = 523–43 | date = September 2016 | pmid = 27250768 | pmc = 4981678 | doi = 10.1128/MMBR.00069-15 }}</ref> The battery was made by engineering [[M13 bacteriophage|M13 bacteriaophages]] so they would coat themselves in [[iron phosphate]] and then assemble themselves along a [[carbon nanotube]]. This created a highly conductive medium for use in a cathode, allowing energy to be transferred quickly. They could be constructed at lower temperatures with non-toxic chemicals, making them more environmentally friendly.<ref>{{cite journal | vauthors = Lee YJ, Yi H, Kim WJ, Kang K, Yun DS, Strano MS, Ceder G, Belcher AM | title = Fabricating genetically engineered high-power lithium-ion batteries using multiple virus genes | journal = Science | volume = 324 | issue = 5930 | pages = 1051–5 | date = May 2009 | pmid = 19342549 | doi = 10.1126/science.1171541 | bibcode = 2009Sci...324.1051L | s2cid = 32017913 | doi-access = free }}</ref>