EEB 180: Genetic Engineering in Developing Countries


GM mosquitoes for disease control


Contents


Background

 

Refractory genes

Transgene confering refractoriness to rodent malaria:

 

Refractory gene

Figure 1: Mosquitoes become infected with the malaria parasite upon taking an infected human blood-meal. This produces an oocyst in the mosquito's gut wall (light red). When the oocyst ruptures, it releases sporozoites that pass through the gut (dark red) and into the hemocoel (white). The sporozoites are then amplified and migrate through the mosquito's body to the salivary glands, ready to infect a new human. Right: The laboratory of Marcelo Jacobs-Lorena at Johns Hopkins University has identified receptor sites for proteins that are necessary for the malaria parasite to pass through the gut wall after the oocyst ruptures. The same receptors are involved with the passage of sporozoites into the salivary glands. The laboratory has produced small proteins that preferentially occupy these sites (blue), blocking transmission of sporozoites through the gut wall and into the salivary glands. The appropriate gene constructs have been introduced into An. stephensi mosquitoes, thus rendering them refractory to P. berghei (a model system for human malaria).

 

Gene drive systems


Requirements of gene drive systems:

 

Transposable elements (TEs)

 

TEs

Figure 2: Two mechanisms by which Class II TEs can replicate. (A) In templated gap repair, excision and transposition leaves a gap that is sometimes sealed by copying information on the homologous chromosome. (B) In S-phase transposition, a replicated TE transposes to an unreplicated part of the genome and is replicated again.

 

Sources of encouragement:

Problems:

 

Homing endonuclease genes (HEGs)

 

HEG

Figure 3: A HEG is found between two specific sequenes of DNA. The HEG produces an endonuclease which cleaves a specific recognition sequence when it is not already filled by another HEG. This gap is then repaired using the homologous chromosome as a template, leading to another copy of the HEG.

 

Attractive features of HEGs:

Disadvantages:

Alternative strategy:

Current research:

 

Medea

Synthetic Medea element:

 

Medea

Figure 4: A punnet square representing the reproductive advantage of the Medea allele. Offspring of females who do not inherit the Medea allele are killed by the maternal toxin because they are not able to express the zygotic antidote. This distorts the offspring ratio in favor of the Medea allele.

 

Attractive features of Medea:

Current research:

 

Ecological considerations


The large number of species of malaria parasites and vectors makes malaria difficult to control genetically:

Even within An. gambiae populations there are barriers to gene flow that must be considered:

 

Population structure of An. gambiae in Africa

Figure 5: Geographic population structure of An. gambiae throughout Africa showing the distribution of chromosomal inversions and molecular forms.

 

Integrated vector management strategies

 

References