Development of a gene drive system for locally confined and reversible population replacement in Aedes aegypti using chromosomal translocations

• Applicant: Dr. Georg Oberhofer
• Subject Area: Evolutionary Cell and Developmental Biology (Zoology)
• Term: from 2015 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 277089463

Aedes aegypti mosquitoes are the main vector for devastating diseases like dengue and yellow fever which are the cause for ten thousands of deaths each year, mainly among children. In the case of dengue fever the infection rates have approximately doubled every ten years since the 1970's, clearly showing that classic approaches using insecticides have failed to suppress the mosquito populations. Hence, novel strategies to control this global epidemic are in dire need.One approach to do this is with gene drive systems. They can be used to replace Aedes populations with strains that block the transmission of viruses. So far not a single gene drive system has been established in Aedes mosquitoes, the goal of the research proposed herein.The drive system I will build is based on chromosomal translocations. If translocation carrying mosquitoes mate into the wild, a proportion of the offspring is unviable due to chromosomal imbalance. This leads to a gradual loss of wildtype chromosomes and fixation of the translocation alleles. Among all the available drive systems, the translocation based drive was chosen because it is evolutionary stable, it does not spread to non-target areas and it can be reversed.To generate Aedes strains carrying translocations, two approaches will be pursued in parallel. First, translocation constructs will be integrated randomly into the Aedes genome with piggyBac transposase, followed by the activation of a linked homing endonuclease that induces double-stranded DNA breaks, which upon repair can form translocations. Second, translocations will be induced with the novel CRISPR/Cas9 system. Finally, the resulting strains will be evaluated in fitness assays and tested for their potential to drive population replacement.

• DFG Programme: Research Fellowships
• International Connection: USA
• Host: Professor Dr. Bruce Hay