Investigating E. coli Strain HT115-mediated RNA Interference in the Treatment of Gastrointestinal Nematode Infection by Ascaris lumbricoides

Nematodes are parasitic worms in the body that can lead to a variety of health problems. One subset of these nematodes are called Ascaris lumbricoides, which proliferate within the intestine. This is the most common worm affecting humans, infecting over hundreds of millions globally. A common method of nematode infection is through contact with soil contaminated with their eggs. This experiment attempts to disrupt the VENOM gene of A. lumbricoides to prevent their function in human hosts and lead to expulsion of the worm. This experiment begins with editing a gut bacterium to deliver RNA interference molecules to target the VENOM gene and lead to parasite expulsion. We propose two delivery methods of secretion: the first is to use the outer membrane vesicles to package and deliver the RNA and the second is to directly secrete the RNAi using a bacterial Type 3 secretion system. We propose that in both methods after the release of the RNAi, it will be absorbed by the worm and downregulate the VENOM gene leading to the worm's death. These findings will be able to provide valuable insight into improving current therapies and potentially give insight on how we can prevent recurrence of nematode infection.