French Stephanie, Da Silva Rachael, Storm Janet, Wastika Christida E, Cullen India, Have Martijn Ten, Hughes Grant L, Modahl Cassandra M
Centre for Snakebite Research and Interventions, Liverpool School of Tropical Medicine, Liverpool, UK.
Departments of Vector Biology and Tropical Disease Biology, Centre for Neglected Tropical Disease, Liverpool School of Tropical Medicine, Liverpool, UK.
Parasit Vectors. 2025 Jan 29;18(1):32. doi: 10.1186/s13071-025-06663-9.
Mosquitoes are responsible for the transmission of numerous pathogens, including Plasmodium parasites, arboviruses and filarial worms. They pose a significant risk to public health with over 200 million cases of malaria per annum and approximately 4 billion people at risk of arthropod-borne viruses (arboviruses). Mosquito populations are geographically expanding into temperate regions and their distribution is predicted to continue increasing. Mosquito symbionts, including fungi, bacteria and viruses, have desirable traits for mosquito disease control including spreading horizontally and vertically through mosquito populations and potentially colonising multiple important vector species. Paratransgenesis, genetic modification of mosquito symbionts with effectors to target the pathogen rather than the vector, is a promising strategy to prevent the spread of mosquito-borne diseases. A variety of effectors can be expressed but venom toxins are excellent effector candidates because they are target specific, potent and stable. However, the only toxins to be explored in mosquito paratransgenesis to date are scorpine and mutated phospholipase A2. To enhance the scope, effectiveness and durability of paratransgenesis, an expanded arsenal of effectors is required. This review discusses other potential toxin effectors for future paratransgenesis studies based on prior in vitro and in vivo antiparasitic and antiviral studies and highlights the need for further research and investment in this area. In terms of mosquito-borne diseases, paratransgenesis strategies have been developed to target Plasmodium. We postulate the potential to apply this principle to target arboviruses using antiviral toxin effectors.
蚊子是多种病原体的传播媒介，包括疟原虫、虫媒病毒和丝虫。它们对公共卫生构成重大风险，每年有超过2亿例疟疾病例，约40亿人面临虫媒病毒感染风险。蚊子种群正在向温带地区地理性扩张，预计其分布还将继续增加。蚊子的共生体，包括真菌、细菌和病毒，具有控制蚊子疾病的理想特性，包括在蚊子种群中水平和垂直传播，并有可能在多种重要病媒物种中定殖。拟转基因，即通过效应子对蚊子共生体进行基因改造以靶向病原体而非病媒，是预防蚊媒疾病传播的一种有前景的策略。可以表达多种效应子，但毒液毒素是优秀的效应子候选物，因为它们具有靶点特异性、高效性和稳定性。然而，迄今为止在蚊子拟转基因中探索的唯一毒素是蝎毒素和突变的磷脂酶A2。为了扩大拟转基因的范围、有效性和持久性，需要更多种类的效应子。本综述基于先前的体外和体内抗寄生虫和抗病毒研究，讨论了未来拟转基因研究的其他潜在毒素效应子，并强调了在该领域进行进一步研究和投资的必要性。就蚊媒疾病而言，已经开发出针对疟原虫的拟转基因策略。我们推测利用抗病毒毒素效应子将这一原理应用于靶向虫媒病毒的潜力。
