At the meeting on November 15 I have covered a paper by Gantz et al. describing a method for creating transgenic mosquitoes expressing antibodies hindering the development of malaria parasites.
The immune system is commonly divided into two categories: innate and adaptive. The innate immune system consists of non-specific defence mechanisms such as epithelial barriers, macrophages etc. The innate system is present in virtually every living organism. The adaptive immune system is responsible for invader-specific defence response. Is consists of B and T lymphocytes and encompasses antibody production. As only vertebrates posses the adaptive immune system, mosquitoes do not naturally produce antibodies which hinders their ability to defend themselves against pathogens such as malaria.
In the study by Gantz et al. the authors inserted transgenes expressing three single-chain Fvs (m4B7, m2A10 and m1C3) into the previously-characterised chromosomal docking sites.
RT-PCR was used to detect scFv transcripts in RNA isolated from the transgenic mosquitoes (see Figure 1). The experiments showed that the attP 44-C recipient line allowed expression of the transgenes coding for the scFvs.
The authors evaluated the impact of the modifications on the fitness of the mosquitoes. It was shown that the transgene expression does not reduce the lifespan of the mosquitoes, or their ability to procreate.
Expression of the scFvs targeted the parasite at both the early and late development stages. The transgenic mosquitoes displayed a significant reduction in the number of malaria sporozoites per infected female, in most cases completely inhibiting the sporozoite development.
Overall the study showed that it is possible to develop transgenic mosquitoes that are resistant to malaria. If this method was combined with a mechanism for a gene spread, the malaria-resistant mosquitoes could be released into the environment, helping to fight the spread of this disease.