Genetically modified virus

A genetically modified virus is a virus that has gone through genetic modification for various biomedical purposes, agricultural purposes, bio-control and technological purposes. Genetic modification involves the insertion or deletion of genes to improve organisms and is usually obtained with biotechnology.

General usage

Genetic modification involves the insertion or deletion of genes into the viral genome to improve organisms and is usually obtained with biotechnology methods. These methods of gene transfer include physically inserting the extra DNA into the nucleus of the intended host with a very small syringe, or with very small particles fired from a gene gun.[1] Other methods exploit natural forms of gene transfer, such as the ability of Agrobacterium to transfer genetic material to plants,[2] or the ability of lentiviruses to transfer genes to animal cells.[3]

 Health applications

Gene therapy

Gene therapy[4] uses genetically modified viruses to deliver genes that can cure diseases in human cells.These viruses can deliver DNA or RNA genetic material to the targeted cells. Gene therapy is also used by inactivating mutated genes that are causing the disease using viruses.[5] Viruses that have been used for gene therapy are, adenovirus, lentivirus, retrovirus and the herpes simplex virus.[6] Although gene therapy is still relatively new, it has had some successes. It has been used to treat inherited genetic disorders such as severe combined immunodeficiency.[7] Although some successes, gene therapy is still considered a risky technique and studies are still undergoing to ensure safety and effectiveness.[5]

Cancer treatment

In 2004, researchers reported that a genetically modified virus that exploits the selfish behaviour of cancer cells might offer an alternative way of killing tumours.[8][9] Since then, several researchers have developed genetically modified oncolytic viruses that show promise as treatments for various types of cancer.[10] [11] [12][13][14]

Vaccines 

In 2001, it was reported that genetically modified viruses can possibly be used to develop vaccines[15] against diseases such as, AIDS, herpes, dengue fever and viral hepatitis by using a proven safe vaccine virus, such as adenovirus, and modify its genome to have genes that code for immunogenic proteins that can spike the immune systems response to then be able to fight the virus.

Heart pacemaker

In 2012, US researchers reported that they injected a genetically modified virus into the heart of pigs. This virus inserted into the heart muscles a gene called Tbx18 which enabled heartbeats. The researchers forecast that one day this technique could be used to restore the heartbeat in humans who would otherwise need electronic pacemakers.[16][17]

 Lentivirus

A genetically modified version of the lentivirus has been used to treat diseases. The lentivirus is versatile and can be used as a genetically modified virus by using it as a vector for gene therapy.[18]

Bio-control

Rabbits

In Spain and Portugal, by 2005 rabbits had declined by as much as 95% over 50 years due diseases such as myxomatosis, rabbit haemorrhagic disease and other causes. This in turn caused declines in predators like the Iberian lynx, a critically endangered species.[19][20] In 2000 Spanish researchers investigated a genetically modified virus which might have protected rabbits in the wild against myxomatosis and rabbit haemorrhagic disease.[21] However, there was concern that such a virus might make its way into wild populations in areas such as Australia and create a population boom.[19][22] Rabbits in Australia are considered to be such a pest that land owners are legally obliged to control them.[23]

 Papayas

Tropical and subtropical regions located in the United States, South America, India, Africa, Mexico, China, and Australia suffered a decline in papaya production due to the papaya ringspot virus (PRSV). To combat this disease PRSV-resistant papaya was genetically engineered through gene technology.[24] PSRV-resistant papayas were engineered by using a protein mediated, RNA-silencing mechanism. This was achieved through an agrobacterium mediated transformation of the papaya. Other methods used to combat the disease are, a gene gun method and post-transcriptional gene silencing technology. Post-transcriptional gene silencing technology is still currently being studied and can possibly be used for treatment of PRSV in the future.

Technological applications

Lithium-ion batteries

In 2009, MIT scientists created a genetically modified virus has been used to construct a more environmentally friendly lithium-ion battery.[25][26][27] The battery was constructed by genetically engineering different viruses such as, the E4 bacteriophage and the M13 bacteriophage, to be used as a cathode. This was done by editing the genes of the virus that code for the protein coat. The protein coat is edited to coat itself in iron phosphate to be able to adhere to highly conductive carbon-nanotubes. The viruses that have been modified to have a multifunctional protein coat can be used as a nano-structured cathode with causes ionic interactions with cations. Allowing the virus to be used as a small battery. Angela Blecher, the scientist who led the MIT research team on the project, says that the battery is powerful enough to be used as a rechargeable battery, power hybrid electric cars, and a number of personal electronics.[28]

Safety concerns and regulation

Bio-hazard research limitations

The National Institute of Health declared a research funding moratorium on select Gain-of-Function virus research in January 2015.[29] Questions about a potential escape of a modified virus from a biosafety lab and the utility of dual-use-technology, dual use research of concern (DURC), prompted the NIH funding policy revision.[30][31]

GMO lentivirus incident

A scientist claims she was infected by a genetically modified virus while working for Pfizer. In her federal lawsuit she says she has been intermittently paralyzed by the Pfizer-designed virus. "McClain, of Deep River, suspects she was inadvertently exposed, through work by a former Pfizer colleague in 2002 or 2003, to an engineered form of the lentivirus, a virus similar to the one that can lead to acquired immune deficiency syndrome, or AIDS."[32] The court found that McClain failed to demonstrate that her illness was caused by exposure to the lentivirus,[33] but also that Pfizer violated whistleblower laws.[34]

References

  1. ↑ Johnston SA, Tang DC (1994). "Gene gun transfection of animal cells and genetic immunization". Methods in Cell Biology. 43 Pt A: 353–365. doi:10.1016/s0091-679x(08)60612-3. OCLC 31189762. PMID 7823871.
  2. ↑ Lee LY, Gelvin SB (February 2008). "T-DNA binary vectors and systems". Plant Physiol. 146 (2): 325–332. doi:10.1104/pp.107.113001. OCLC 1642351. PMC 2245830. PMID 18250230.
  3. ↑ Park F (October 2007). "Lentiviral vectors: are they the future of animal transgenesis?". Physiol. Genomics. 31 (2): 159–173. doi:10.1152/physiolgenomics.00069.2007. OCLC 37367250. PMID 17684037.
  4. ↑ Selkirk SM (October 2004). "Gene therapy in clinical medicine". Postgrad Med J. 80 (948): 560–70. doi:10.1136/pgmj.2003.017764. PMC 1743106. PMID 15466989.
  5. 1 2 Reference, Genetics Home. "What is gene therapy?". Genetics Home Reference. Retrieved 2017-12-08.
  6. ↑ Hassan, Memy H.; Othman, Essam E.; Hornung, Daniela; Al-Hendy, Ayman (2009-08-10). "Gene therapy of benign gynecological diseases". Advanced drug delivery reviews. 61 (10): 822–835. doi:10.1016/j.addr.2009.04.023. ISSN 0169-409X. PMC 4477532. PMID 19446586.
  7. ↑ Cavazzana-Calvo M, Fischer A (June 2007). "Gene therapy for severe combined immunodeficiency: are we there yet?". J. Clin. Invest. 117 (6): 1456–65. doi:10.1172/JCI30953. PMC 1878528. PMID 17549248.
  8. ↑ Genetically-modified virus explodes cancer cells
  9. ↑ GM virus shrinks cancer tumours in humans
  10. ↑ Leja, J.; Yu, D.; Nilsson, B.; Gedda, L.; Zieba, A.; Hakkarainen, T.; Åkerström, G.; Öberg, K.; Giandomenico, V.; Essand, M. (2011). "Oncolytic adenovirus modified with somatostatin motifs for selective infection of neuroendocrine tumor cells". Gene Therapy. 18 (11): 1052–1062. doi:10.1038/gt.2011.54. PMID 21490682.
  11. ↑ Perett, Linda (30 June 2011) Measles viruses genetically modified to treat ovarian cancer National Cancer Institute, Benchmarks, Retrieved 5 September 2012
  12. ↑ Breitbach, CJ; Thorne, SH; Bell, JC; Kirn, DH (2011). "Targeted and Armed Oncolytic Poxviruses for Cancer: The Lead Example of JX-594". Current Pharmaceutical Biotechnology. 13: 1768–1772. doi:10.2174/138920112800958922. PMID 21740365.
  13. ↑ Beasley, Deena (31 August 2011) Cancer-fighting virus shown to target tumors alone Reuters Science, Retrieved 5 September 2012
  14. ↑ Garber, K. (2006). "China Approves World's First Oncolytic Virus Therapy for Cancer Treatment". JNCI Journal of the National Cancer Institute. 98 (5): 298–300. doi:10.1093/jnci/djj111. PMID 16507823.
  15. ↑ Stephenson, J. R. (March 2001). "Genetically modified viruses: vaccines by design". Current Pharmaceutical Biotechnology. 2 (1): 47–76. ISSN 1389-2010. PMID 11482348.
  16. ↑ Gallagher, James (16 December 2012) Virus rebuilds heart's own pacemaker in animal tests BBC News Health, Retrieved 5 January 2013
  17. ↑ Kapoor, N.; Liang, W.; Marbán, E.; Cho, H. C. (2012). "Direct conversion of quiescent cardiomyocytes to pacemaker cells by expression of Tbx18". Nature Biotechnology. 31: 54–62. doi:10.1038/nbt.2465. PMC 3775583. PMID 23242162.
  18. ↑ Howarth, Joanna L.; Lee, Youn Bok; Uney, James B. (February 2010). "Using viral vectors as gene transfer tools (Cell Biology and Toxicology Special Issue: ETCS-UK 1 day meeting on genetic manipulation of cells)". Cell Biology and Toxicology. 26 (1): 1–20. doi:10.1007/s10565-009-9139-5. ISSN 0742-2091. PMC 2817806. PMID 19830583.
  19. 1 2 Ward, Dan (2005)Reversing Rabbit Decline One of the biggest challenges for nature conservation in Spain and Portugal University of Alberta, Canada, Retrieved 30 August 2012
  20. ↑ Ward, Dan (December 2008). "LynxBrief" (PDF). Retrieved August 2012. Check date values in: |accessdate= (help)
  21. ↑ Bárcena, J.; Morales, M.; Vázquez, B.; Boga, J. A.; Parra, F.; Lucientes, J.; Pagès-Manté, A.; Sánchez-Vizcaíno, J. M.; Blasco, R.; Torres, J. M. (2000). "Horizontal transmissible protection against myxomatosis and rabbit hemorrhagic disease by using a recombinant myxoma virus". Journal of Virology. 74 (3): 1114–1123. doi:10.1128/JVI.74.3.1114-1123.2000. PMC 111445. PMID 10627521.
  22. ↑ Angulo, E.; Gilna, B. (2008). "When biotech crosses borders". Nature Biotechnology. 26 (3): 277–282. doi:10.1038/nbt0308-277. PMID 18327233.
  23. ↑ Catalyst: GM Virus - ABC TV Science
  24. ↑ Azad, Md. Abul Kalam; Amin, Latifah; Sidik, Nik Marzuki (2014). "Gene Technology for Papaya Ringspot Virus Disease Management". The Scientific World Journal. 2014: 1–11. doi:10.1155/2014/768038. ISSN 2356-6140.
  25. ↑ Lee, Yun Jung; Yi, Hyunjung; Kim, Woo-Jae; Kang, Kisuk; Yun, Dong Soo; Strano, Michael S.; Ceder, Gerbrand; Belcher, Angela M. (2009-05-22). "Fabricating Genetically Engineered High-Power Lithium-Ion Batteries Using Multiple Virus Genes". Science. 324 (5930): 1051–1055. doi:10.1126/science.1171541. ISSN 0036-8075. PMID 19342549.
  26. ↑ http://web.mit.edu/newsoffice/2009/virus-battery-0402.html New virus-built battery could power cars, electronic devices
  27. ↑ Hidden Ingredient In New, Greener Battery: A Virus
  28. ↑ "New virus-built battery could power cars, electronic devices". MIT News. Retrieved 2017-12-11.
  29. ↑ U.S. Government (October 17, 2014). "U.S. Government Gain-of-Function Deliberative Process and Research Funding Pause on Selected Gain-of-Function Research Involving Influenza, MERS, and SARS Viruses" (PDF).
  30. ↑ Berg, Paul (14 September 2012). "The Dual-Use Conundrum". Science. 337 (6100): 1273. doi:10.1126/science.1229789. PMID 22984033.
  31. ↑ "Biosecurity - Dual Use Research of Concern". NIH Office of Science Policy (OSP).
  32. ↑ "Ex-Pfizer Worker Cites Genetically Engineered Virus In Lawsuit Over Firing". Courant.com. March 14, 2010. Retrieved July 11, 2011.
  33. ↑ "McClain v. PFIZER, INC., 692 F. Supp. 2d 229". Retrieved September 13, 2012.
  34. ↑ "A Pfizer Whistle-Blower Is Awarded $1.4 Million". The New York Times. April 2, 2010. Retrieved September 13, 2012.
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