Transduction of Schistosoma mansoni using Boudicca, an endogenous retrotransposon of schistosomes

引起血吸虫病的血吸虫在76个国家流行;据估计，多达3亿人受到感染，另有6亿人生活在感染的危险之中。这种寄生蠕虫存款卵进入人体肠道和肝脏的血管，引起慢性炎症。这种疾病只造成一小部分患者死亡，但长期的疼痛和痛苦给发展中国家造成的巨大经济负担超过了大多数其他地方病。控制主要依靠吡喹酮药物，但其广泛使用导致人们担心会产生耐药性。不久将需要新的药物或控制策略。1994年，世界卫生组织发起了血吸虫基因组计划，旨在确定靶基因，使科学家能够开发新的药物和疫苗。预计蠕虫的完整基因组将在未来12个月内报告，并且迫切需要确定每个基因在可能成为旨在杀死寄生虫的药物和疫苗的良好候选人的途径中的重要性的方法。在这项研究中，我们将使用一个内源性逆转录转座子，我们已经确定在寄生虫作为一种工具，以遗传操纵蠕虫。这将有助于理解基因组计划发现的新抗原的功能和重要性。为了测试这种方法，我们将使用RNA干扰（RNAi）来分析基因功能。该技术采用了一种天然存在的途径，该途径使用短RNA分子来非常特异地控制基因产物的形成。我们建议构建病毒样元件来递送这些RNA。吸虫以血液为食，我们将抑制关键的消化酶，以确定它们是否可能成为药物和疫苗的有效靶点。在公共卫生方面，这项调查旨在建立新的方法，以帮助开发新的疗法来治疗和控制血吸虫病。

Blood flukes that cause schistosomiasis are endemic in 76 countries; it is estimated that as many as 300 million people are infected, and that another 600 million live at risk of infection. The parasitic worms deposit eggs into the blood vessels of the human gut and liver causing chronic inflammation. The disease kills only a small proportion of patients however the long-term pain and suffering creates a huge economic burden on developing countries that surpasses that of most other endemic diseases. Control largely relies on the drug praziquantel however its wide scale use has led to concerns that drug resistance will develop. New Drugs or control strategies will soon be required. In 1994 the World Health Organisation Schistosome Genome Project was initiated aiming at identifying target genes that will enable scientists to develop new drugs and vaccines. It is anticipated the complete genome of the worm will be reported within the next 12 months and methods are desperately needed to determine the importance of each gene in the pathways that may make good candidates for drugs and vaccines aimed at killing the parasite. In this study we will use an endogenous retrotransposon that we have identified in the parasite as a vehicle to genetically manipulate the worm. This will help to understand the function and importance of novel antigens that have been discovered by the genome project. To test this method we will use RNA interference (RNAi) to analyse gene function. This technology employs a naturally occurring pathway that uses short RNA molecules to very specifically control the formation of gene products. We propose to construct virus-like elements to deliver these RNAs. The flukes feed on blood and we will inhibit key digestive enzymes to determine if they might make effective targets for drugs and vaccines. In terms of public health, this investigation seeks to establish novel methods to aid the development of new therapies to treat and control schistosomiasis.