• Le 29 novembre 2017
  • à 11h00

« CRISPR based gene drive solutions for the control of diseases vectors »

Andrea CRISANTI is professor of molecular parasitology at Imperial College, graduated in Medicine at the University of Rome "la Sapienza' and carried his doctoral work at the Basel Institute for Immunology. Prof. Crisanti has also been appointed full professor of Microbiology and Clinical Microbiology at the University of Perugia where until recently has coordinated the Centre of Functional Genomics. He 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. These include: i) the identification of the molecules involved in mosquito gut meal digestion; ii) the characterization of key genes involved in plasmodium molecular motor; iii) the development of gene transfer technology for anopheline mosquitoes; iv) the establishment of gene drive technology in mosquitoes; and v) the development of synthetic sex distorter producing male only progeny. The development of gene drive technology promises to overcome many of the roadblocks that so far have hampered the eradication of malaria in resource poor countries. We have utilized this technology to spread genetic modifications impairing mosquito reproductive capability either targeting genes involved in female fertility of inducing male sex bias in the progeny. This works using a class of engineered enzymes that cut unique DNA sequences known as homing endonucleases (HEG) at defined chromosomal locations. During meiosis the cleavage site is repaired by homologous recombination using as template the allele carrying the HEG thereby increasing the frequency of the genetic modification in the progeny. We demonstrated that the activity of HEG is not due to intrinsic biological properties of the enzymes. Any endonuclease (TALEN or Zinc finger) placed in the right chromosomal location with the correct specificity for the corresponding site on the unmodified allele can function as drive. This provided the rationale to exploit the CRISPER/Cas9 nuclease to develop a genetic drive targeting female fertility genes that spread into caged mosquito populations. HEG and CRISPER/cas9 nuclease could also be used to manipulate the sex ratio of mosquitoes. This has been achieved by introducing nucleases that selectively shreds the X chromosome during sperm cell formation thereby generating a mosquito line that produces male gametes only.