Paratransgenesis

Paratransgenesis is a technique that attempts to eliminate a pathogen from vector populations through transgenesis of a symbiont of the vector. The goal of this technique is to control vector-borne diseases. The first step is to identify proteins that prevent the vector species from transmitting the pathogen. The genes coding for these proteins are then introduced into the symbiont, so that they can be expressed in the vector. The final step in the strategy is to introduce these transgenic symbionts into vector populations in the wild.

The first example of this technique used Rhodnius prolixus which is associated with the symbiont Rhodococcus rhodnii. R. prolixus is an important insect vector of Chagas disease that is caused by Trypanosoma cruzi. The strategy was to engineer R. rhodnii to express proteins such as Cecropin A that are toxic to T. cruzi or that block the transmission of T. cruzi.[1]

Attempts are also made in Tse-tse flies using bacteria[2][3] and in malaria mosquitoes using fungi,[4] viruses,[5] or bacteria.[6]

In order to perform paratransgenesis, there are several requirements:

  • The symbiotic bacteria can be grown in vitro easily.
  • They can be genetically modified, such as through transformation with a plasmid containing the desired gene.
  • The engineered symbiont is stable and safe.
  • The association between vector and symbiont cannot be attenuated.
  • Field delivery is easily handled.

References
  1. Durvasula, R.V., Gumbs, A., Panackal, A., Kruglov, O., Aksoy, S., Merrifield, R.B., Richards, F.F., and Beard, C.B. (1997). Prevention of insect-borne disease: an approach using transgenic symbiotic bacteria. Proc. Natl. Acad. Sci. U. S. A. 94, 3274-3278.
  2. Aksoy, S; Weiss, B; Attardo, G (2008). "Paratransgenesis applied for control of tsetse transmitted sleeping sickness". Advances in Experimental Medicine and Biology. 627: 35–48. doi:10.1007/978-0-387-78225-6_3. ISBN 978-0-387-78224-9. PMID 18510012.
  3. De Vooght L, Caljon G, Stijlemans B, De Baetselier P, Coosemans M, Van den Abbeele J (Feb 15, 2012). "Expression and extracellular release of a functional anti-trypanosome Nanobody® in Sodalis glossinidius, a bacterial symbiont of the tsetse fly". Microbial Cell Factories. 11: 23. doi:10.1186/1475-2859-11-23. PMC 3311065. PMID 22335892.
  4. Fang, W; Vega-Rodríguez, J; Ghosh, AK; Jacobs-Lorena, M; Kang, A; St Leger, RJ (Feb 25, 2011). "Development of transgenic fungi that kill human malaria parasites in mosquitoes". Science. 331 (6020): 1074–7. Bibcode:2011Sci...331.1074F. doi:10.1126/science.1199115. PMC 4153607. PMID 21350178.
  5. Ren, X; Hoiczyk, E; Rasgon, JL (Aug 22, 2008). "Viral paratransgenesis in the malaria vector Anopheles gambiae". PLOS Pathogens. 4 (8): e1000135. doi:10.1371/journal.ppat.1000135. PMC 2500179. PMID 18725926.
  6. Rodrigues FG, Santos MN, de Carvalho TX, Rocha BC, Riehle MA, Pimenta PF, Abraham EG, Jacobs-Lorena M, Alves de Brito CF, Moreira LA (Apr 2008). "Expression of a mutated phospholipase A2 in transgenic Aedes fluviatilis mosquitoes impacts Plasmodium gallinaceum development". Insect Molecular Biology. 17 (2): 175–83. doi:10.1111/j.1365-2583.2008.00791.x. PMC 4137777. PMID 18353106.
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