Deliverance from Dengue Fever?

Dengue fever is a deadly disease caused by mosquito bites (primarily the species Aedes aegypt), and its prevalence in the world is increasing rapidly. Symptoms of dengue vary and include fever, severe headache, muscular and joints pain or skin rashes. In some cases, a deadly complication occurs resulting in dengue haemorrhagic fever (DHF). DHF can lead to circulatory failure and shock due to blood pressure falling, resulting in death.

The World Health Organisations (WHO) reports that dengue fever is endemic, always present in a population, in over 100 countries with half a million people each year requiring hospitalization due to DHF, 2.5% of which die. The incidents of disease are increasing as mosquito populations in urban environments continue to increase at a dangerous rate. Despite the wide-spread nature of the disease, no vaccinations exist at present.

However, help is at hand as a Research Team from Oxitec, an off shoot from the Oxford Univeristy, have utilised genetic modification to introduce a new gene into male mosquitoes which causes them to produce offspring that die when becoming pupae. Genetically Modified (GM) males will hence not breed effectively and therefore fewer mosquitos will be produced each generation. Fewer mosquitoes equals less dengue transmission.

How does the genetic modification cause death in the mosquito offspring? The answer lies in the “repressible lethal genetic system” contained in the gene introduced. The lethal genetic system in this instance is a gene known as the tetracycline-controlled Transcription Activator (tcTA). The tcTA gene encodes for a protein which when expressed binds to the tcTA gene and causes production of more tcTA protein, which binds to the tcTA gene causing production of more tcTA protein. A positive feedback loop occurs as the levels of TA protein continue to rise until the mosquito’s food stores are depleted and it dies.

A similar strategy has been utilised in other infection spreading insects, however instead of genetic modification the males were exposed to radiation leading to sterilisation. Breeding still occurred but no offspring were successfully reduced, reducing the population size. This is not viable for mosquitoes since the irradiated males are too physically weak to compete with other males during mating. The tcTA system overcomes this, as the tcTA protein also binds the chemical tetracycline. If bound to tetracycline it cannot bind to DNA and therefore no positive feedback loops occurs. Offspring will inherit the fully functioning tcTA gene without tetracycline and will die.

This method depends on the GM mosquitoes’ ability to breed successfully. Oxitec trialled the system in 2009, releasing which made up 16% of the breeding population into the Cayman Islands. Recently the eggs were collected and tested for the presence of the tcTA gene. It was found that 10% of the eggs collected contained the TA gene demonstrating that GM males are therefore able to breed, if not as well as the natural males. This result shows that lethal genetic modification can be passed on and offers a possible solution for dengue fever.