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   PID: hpt/lnx 1.9.0-cur 2019-01-08   
   TID: hpt/lnx 1.9.0-cur 2019-01-08   
    New genetic technology developed to halt malaria-spreading mosquitoes   
    As envisioned, first-of-its-kind African mosquito suppression system   
   would reduce child mortality and aid economic development    
      
     Date:   
         July 5, 2023   
     Source:   
         University of California - San Diego   
     Summary:   
         Using CRISPR technology, scientists have engineered a new way   
         to genetically suppress populations of Anopheles gambiae, the   
         mosquitoes that primarily spread malaria in Africa and contribute   
         to economic poverty in affected regions.   
      
      
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   FULL STORY   
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   Malaria remains one of the world's deadliest diseases. Each year   
   malaria infections result in hundreds of thousands of deaths, with the   
   majority of fatalities occurring in children under five. The Centers   
   for Disease Control and Prevention recently announced that five cases   
   of mosquito-borne malaria were detected in the United States, the first   
   reported spread in the country in two decades.   
      
   Fortunately, scientists are developing safe technologies to stop the   
   transmission of malaria by genetically editing mosquitoes that spread   
   the parasite that causes the disease. Researchers at the University   
   of California San Diego led by Professor Omar Akbari's laboratory have   
   engineered a new way to genetically suppress populations of Anopheles   
   gambiae, the mosquitoes that primarily spread malaria in Africa and   
   contribute to economic poverty in affected regions. The new system   
   targets and kills females of the A. gambiae population since they bite   
   and spread the disease.   
      
   Publishing July 5 in the journal Science Advances, first-author Andrea   
   Smidler, a postdoctoral scholar in the UC San Diego School of Biological   
   Sciences, along with former master's students and co-first authors   
   James Pai and Reema Apte, created a system called Ifegenia, an acronym   
   for "inherited female elimination by genetically encoded nucleases to   
   interrupt alleles." The technique leverages the CRISPR technology to   
   disrupt a gene known as femaleless (fle) that controls sexual development   
   in A. gambiae mosquitoes.   
      
   Scientists at UC Berkeley and the California Institute of Technology   
   contributed to the research effort.   
      
   Ifegenia works by genetically encoding the two main elements of CRISPR   
   within African mosquitoes. These include a Cas9 nuclease, the molecular   
   "scissors" that make the cuts and a guide RNA that directs the system to   
   the target through a technique developed in these mosquitoes in Akbari's   
   lab. They genetically modified two mosquito families to separately   
   express Cas9 and the fle-targeting guide RNA.   
      
   "We crossed them together and in the offspring it killed all the female   
   mosquitoes," said Smidler, "it was extraordinary." Meanwhile, A. gambiae   
   male mosquitoes inherit Ifegenia but the genetic edit doesn't impact their   
   reproduction. They remain reproductively fit to mate and spread Ifegenia.   
      
   Parasite spread eventually is halted since females are removed and the   
   population reaches a reproductive dead end. The new system, the authors   
   note, circumvents certain genetic resistance roadblocks and control   
   issues faced by other systems such as gene drives since the Cas9 and   
   guide RNA components are kept separate until the population is ready to   
   be suppressed.   
      
   "We show that Ifegenia males remain reproductively viable, and can   
   load both flemutations and CRISPR machinery to induce flemutations in   
   subsequent generations, resulting in sustained population suppression,"   
   the authors note in the paper. "Through modeling, we demonstrate that   
   iterative releases of non- biting Ifegenia males can act as an effective,   
   confinable, controllable and safe population suppression and elimination   
   system."  Traditional methods to combat malaria spread such as bed nets   
   and insecticides increasingly have been proven ineffective in stopping   
   the disease's spread.   
      
   Insecticides are still heavily used across the globe, primarily in an   
   effort to stop malaria, which increases health and ecological risks to   
   areas in Africa and Asia.   
      
   Smidler, who earned a PhD (biological sciences of public health) from   
   Harvard University before joining UC San Diego in 2019, is applying her   
   expertise in genetic technology development to address the spread of   
   the disease and the economic harm that comes with it. Once she and her   
   colleagues developed Ifegenia, she was surprised by how effective the   
   technology worked as a suppression system.   
      
   "This technology has the potential to be the safe, controllable and   
   scalable solution the world urgently needs to eliminate malaria once   
   and for all," said Akbari, a professor in the Department of Cell   
   and Developmental Biology. "Now we need to transition our efforts   
   to seek social acceptance, regulatory use authorizations and funding   
   opportunities to put this system to its ultimate test of suppressing   
   wild malaria-transmitting mosquito populations. We are on the cusp of   
   making a major impact in the world and won't stop until that's achieved."   
   The researchers note that the technology behind Ifegenia could be adapted   
   to other species that spread deadly diseases, such as mosquitoes known to   
   transmit dengue (break-bone fever), chikungunya and yellow fever viruses.   
      
   The full author list includes Andrea Smidler, James Pai, Reema Apte,   
   Hector Sanchez C., Rodrigo Corder, Eileen Jeffrey Gutierrez, Neha Thakre,   
   Igor Antoshechkin, John Marshall and Omar Akbari.   
      
       * RELATED_TOPICS   
             o Health_&_Medicine   
                   # Malaria # Diseases_and_Conditions # Ebola # Genes   
             o Plants_&_Animals   
                   # Insects_(including_Butterflies) # Pests_and_Parasites #   
                   Biochemistry_Research # CRISPR_Gene_Editing   
       * RELATED_TERMS   
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   Journal Reference:   
      1. Andrea L. Smidler, James J. Pai, Reema A. Apte, He'ctor M. Sa'nchez   
      C.,   
         Rodrigo M. Corder, Eileen Jeffrey Gutie'rrez, Neha Thakre, Igor   
         Antoshechkin, John M. Marshall, Omar S. Akbari. A confinable   
         female- lethal population suppression system in the malaria   
         vector, Anopheles gambiae. Science Advances, 2023; 9 (27) DOI:   
         10.1126/sciadv.ade8903   
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   Link to news story:   
   https://www.sciencedaily.com/releases/2023/07/230705154012.htm   
      
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