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

导致血吸虫病的血吸虫在76个国家流行；估计有多达3亿人感染，另有6亿人生活在感染风险中。寄生虫将卵子沉积到人体肠道和肝脏的血管中，导致慢性炎症。这种疾病只导致一小部分患者死亡，但长期的痛苦和苦难给发展中国家造成了巨大的经济负担，超过了大多数其他地方性疾病。控制在很大程度上依赖于药物吡喹酮，然而，它的广泛使用导致了人们对抗药性将会发展的担忧。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项目，旨在确定目标基因，使科学家能够开发新的药物和疫苗。预计这种蠕虫的完整基因组将在未来12个月内公布，迫切需要各种方法来确定每个基因在可能成为杀死这种寄生虫的药物和疫苗的良好候选者的途径中的重要性。在这项研究中，我们将使用我们在寄生虫中鉴定的内源性反转录转座子作为载体来对蠕虫进行遗传操作。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。这项技术采用了一种自然发生的途径，使用短RNA分子非常专门地控制基因产物的形成。我们建议构建类似病毒的元件来传递这些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，这项调查寻求建立新的方法，以帮助开发治疗和控制血吸虫病的新疗法。

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.