SUMMARY Genetics-based vector control holds great promise in combating vector transmitted diseases. Such a promising strategy, however, has not yet been tested in any vector snail control program of schistosomiasis, one of the world’s most devastating parasitic diseases. The key reason is the lack of a germline delivery technology for delivering genetic materials into gametes or embryos. The inability to deliver genetic materials into snail germline cells is due to the complex anatomical structure of its gametes, the exceedingly small size of its eggs, and its unusual reproductive system, which preclude the application of all existing, well-developed genetic delivery technologies. To circumvent these limitations, we propose an innovative approach that exploits snail yolk proteins as vehicles for shuttling genetic materials into growing oocytes via the natural process of receptor- mediated endocytosis during vitellogenesis. Two types of the most promising snail yolk proteins, yolk ferritin and vitellogenin, both found present in the genome of the schistosomiasis vector snail Biomphalaria glabrata, will be investigated. We will first identify a highly efficient oocyte receptor-binding ligand from snail yolk ferritin or vitellogenin (Aim1) and then test the identified ligand in delivering clustered regularly interspaced short palindromic repeats (CRISPR) cargo into the oocytes for germline modification (Aim 2). This study will open an exciting door for all genetic manipulation studies for basic and applied research of schistosomiasis.

PUBLIC HEALTH RELEVANCE Snail control has been proven to be one of the most effective means for control of schistosomiasis, a neglected tropical disease that currently afflicts 229 million people around the world. Developing germline delivery technology, as proposed in the project, is the first step towards developing innovative snail-targeted genetic strategies for intervention of schistosomiasis transmission.