Need for a Kill Switch
By inserting genes into C. elegans that enable it to identify and degrade harmful environmental toxins, we also risk making the engineered organism better suited for its environment than the native C. elegans strains. The modified strain may become invasive due to its enhanced chemotaxis and digestive abilities that may make it better at finding and digesting different foods or evading dangers. In essence, they have the potential to act as invasive alien species to the ecosystem, and once established, they have the potential to transfer to other ecosystems as well. Since our chemotaxis system is designed to target pollutants, it may also target other bacteria responsible for degrading pollutants and have an overall negative effect on remediation. In addition, human health concerns are another issue.
The creation of a novel-phenotype species comes with unknown risks about their pathogenesis. While it is unlikely that C. elegans can cause human pathogenesis (soil dwelling, nonparasitic nematode), it is not entirely out of the question, as other nematodes (such as those of the superfamily Filarioidea) are classified as parasitic, using humans as their host and causing disease.
Thus, to prevent these and other potential issues, we seek to design a genetic hinderance or “kill-switch” that will prevent the propagation of our modified worm. In C. elegans, several types of kill switch have been proposed, however only two of these methods will be expanded upon:
1. the MRT-2 mutant Kill Switch
2. the RNAi Kill Switch
References
1. Ahmed S, Hodgkin J. (2000) MRT-2 checkpoint protein is required for germline immortality and telomere replication in C. elegans. Nature, 403:159-164
2. Smelick C, Ahmed S. (2005) Achieving immortality in the C. elegans germline. Ageing Research Reviews, 4(1):67-82
3. Telomere Shortening and Damage (2009) (http://www.immortalhumans.com/telomere-shortening-and-damage/)
4. Fire A, Xu S, Montgomery MK, Kostas SA, Driver SE, Mello CC. (1998) Potent and specific genetic interference by double-stranded RNA in Caenorhabditis elegans. Nature, 391(6669):806-11
5. Tabara H, Grishok A, Mello CC. (1998) RNAi in C. elegans: soaking in the genome sequence. Science, 282(5388):430-1
6. Timmons L, Fire A. (1998) Specific interference by ingested dsRNA. Nature, 395(6705):854
7. Timmons L. (2006) Construction of Plasmids for RNA Interference and In Vitro Transcription of Double-Stranded RNA. Methods Mol Biol. 351:109-17.
8. Simmer F, Tijsterman M, Parrish S, Koushika SP, Nonet ML, Fire A, Ahringer J, Plasterk RHA. (2002) Loss of the Putative RNA-Directed RNA Polymerase RRF-3 Makes C. elegans Hypersensitive to RNAi. Current Biology, 12(15): 1317-1319.
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