Editing population genetics for vector control

Abstract
Mosquitoes species of the genus Aedes and Anopheles are responsible for transmitting severe and life threatening diseases including a number of viral encephalitis, Dengue yellow fever, Malaria and more recently Zika. A few Anopheles species are responsible for causing 200 million cases of malaria every year and the death of half a million children under the age of five in less developed regions of Africa. During the last twenty years a worldwide concerted effort based on the use of bed nets, insecticides and drug treatment has halved malaria morbidity and mortality. The implementation of these control measures necessitates about 10 billion per year mostly in the form of donations thus questioning the long-term sustainability of this approach and its suitability for eradicating the disease in the next 30-40 years. The vectorial capacity of a mosquito species to transmit malaria depends on genetically determined traits such as feeding behaviour, longevity, density and ability to support parasite development. Editing of the corresponding genes is anticipated to impair mosquito ability to transmit malaria. The recent development of CRISPR/CAS9 based gene drive technology has unlocked the possibility to selectively edit a mosquito population. Genetic modifications designed to either impair female fertility or interfere with mosquito ability to transmit the malaria parasite have been spread from few laboratory individual to large caged mosquito populations. These laboratory experiments have also supported mathematical modelling predicting how gene technology has the potential to eradicate malaria transmission in a span of few years from vast regions of Africa. Technical challenges in the development of a gene drive technology suitable for release include the development nuclease-resistant functional gene variant that would block the spreading of the drive as well as off target activity of the CAS9 nuclease that may generate undesirable mutations at other loci. We present here a number of solutions to overcome these problems.

 

Biosketch
Andrea Crisanti is professor of molecular parasitology at Imperial College and Professor of Clinical Microbiology at the University of Perugia, Italy. He graduated in Medicine at the University of Rome “la Sapienza’, and carried his doctoral work at the Basel Institute for Immunology. After the doctorate he was awarded a three years EMBO fellowship at the University of Heidelberg, Germany. Thereafter he was employed as medical consultant at the University of Rome Institute of Parasitology. Prof. Crisanti has pioneered the molecular biology of the human malaria vector Anopheles gambiae and has made a number of important scientific contributions that advanced the genetic and molecular knowledge of the malaria parasite and its mosquito vector. More recently Prof. Crisanti has applied concepts of synthetic biology for the development of genetic vector control measures aimed at either eliminating wild type mosquito populations or at interfering with their ability to transmit malaria. This resulted in the development and validation of a CRISPR based genetic drive system capable of spreading, into wild type mosquitoes, mutations impairing female fertility genes. The development of gene drive is generating a growing scientific interest as well as the attention of policy makers, media and pressure groups as a consequence of its implication in manipulating the genetic make up of wild species. Prof Crisanti has been employed at Imperial College for twenty years there he served as head of the section of Infection and Immunity and in the staff promotion committee. In 2001 he was offered the position of Professor of Clinical Microbiology at the University of Perugia. At the university of Perugia, Prof. Crisanti directed the doctorate school for infectious diseases and immunity. There he created the first centre of functional genomics in Italy that he directed until the end of 2015.