The Mosquito, Synthetic Biology, CRISPR, and Malaria
Using Gene Modification and Gene Drive to Eradicate a Disease
Sponsored by PSW Member Tim Thomas
Population alteration strategies based on transgenic mosquitoes carrying genes that prevent parasite transmission have a role in the malaria eradication agenda. They can consolidate elimination gains by providing barriers to parasite and competent vector reintroduction, and allow resources to be focused on new sites while providing confidence that treated areas will remain malaria-free.
A promising strategy for combating malaria is based on harnessing gene drive systems to spread anti-malarial genes throughout mosquito populations rendering them unable to transmit the parasites. Highly-effective anti-malarial gene cassettes that result in a 100% block in mosquitos of Plasmodium falciparum, the most deadly human malaria parasite, were linked to a gene-drive system based on CRISPR/Cas9 biology, and in laboratory experiments using gene drive spread with 99.5% efficiency in Anopheles stephensi mosquitos, the major malarial mosquito vector in urban India.
Challenges remain to be overcome before deploying the system against malaria outside the laboratory. Efficacy and safety have to be demonstrated in carefully controlled field trials. Strategic planning in selecting field-sites, engineered mosquito strains, trial designs and implementation strategies will be required to achieve a successful first field trial of this technology. Furthermore, the trials should use local scientists and adhere to stringent community engagement and regulatory standards. And trials should have an epidemiological endpoint that results in local disease elimination.
About the Speaker
Anthony A. James is Distinguished Professor of Microbiology & Molecular Genetic, and Molecular Biology & Biochemistry in the Schools of Medicine and Biological Sciences, respectively, at the University of California, Irvine. Previously, he was a member of the faculty of the Harvard School of Public Health.
Anthony works on vector-parasite interactions, mosquito molecular biology, and other problems in insect developmental biology. His research emphasizes the use of genetic and molecular-genetic tools to develop synthetic approaches to interrupting pathogen transmission by mosquitoes.
He is an author on more than 170 papers, reviews and policy documents. He was a founding editor of the journal Insect Molecular Biology, and has served on the editorial boards of PLoS Neglected Tropical Diseases, Experimental Parasitology and Entomological Research.
He is active in graduate teaching and mentoring and has guided over 34 graduate students and postdoctoral fellows.
In addition to being elected to the National Academy of Sciences, Anthony has received numerous awards including the UC-Irvine Medal, the Nan-Yao Su Award for Innovation and Creativity in Entomology from the Entomological Society of America, the Premio de Investgación Médica Dr. Jorge Rosenkranz, the Burroughs-Wellcome New Initiatives in Malaria Award and the Burroughs-Wellcome Scholar Award in Molecular Parasitology. He also is an elected Fellow of the Royal Entomological Society of London, the American Association for the Advancement of Science, the Entomological Society of America and the American Society of Tropical Medicine and Hygiene
Anthony earned a BS and a PhD at UC-Irvine, and did postdoctoral work at Harvard Medical School and at Brandeis University.