| 摘要 |
Culicinae mosquito vectors are responsible for the transmission of many deadly arboviruses as dengue fever virus, yellow fever virus, Chikungunya virus, West Nile virus, St. Louis encephalitis virus as well as several filarial nematodes. However, introduction of new desired genes into natural mosquito populations is still very challenging due to the lack of suitable gene drive mechanisms. Anti-pathogen genes or genetic recombination factors encoding for certain vaccines can be inserted into and successfully expressed from the Culicinae mosquito genomes when using the molecular techniques. However, they are more likely to be eliminated from the population due to the resulting fitness cost. Simply releasing such genetically modified strains of mosquitoes into the wild will not curtail disease transmission unless the new genes can spread and increase in the natural environment. This will only occur if the introduced anti-pathogen or vaccine genes confer, or are linked to genes that confer, higher fitness to the individuals bearing them, or if they are linked to other genes that increase in frequency through super-Mendelian inheritance. The invention of the Tra-2 RNAi system which leads to the production of up to 100% male progeny and would have double the Mendelian frequency advantage over wild males has created such a powerful drive system (Kim P. H. and Thanh D. H. 201 1; PCTA/N2011/000011 submitted on 29/12/2011: Culicinae mosquito Tra-2 RNAi, a method to genetically produce maleness populations). Theoretically, this system would drive whole populations to a male-only state and thus extinction. In such circumstances, any genetic factor which could resist the male bias effect of the Tra-2 RNAi constructs would be positively selected for and quickly become widespread throughout the whole population. This invention explores the use of the RNAi technique to repress the activity of the tTA gene in the Tra-2 RNAi construct using a†TA RNAi construct; the tTA RNAi construct turns off the male biasing effect and restores progeny back to a 1 :1 sex ratio. The tTA RNAi repressor constructs are favorably selected for and can be used as a vehicle to carry desirable introduced genes into natural populations. |
