Research progress and limitation analysis of RNA interference in Haemonchus contortus in China

Abstract

Haemonchus contortus is a highly pathogenic and economically important parasitic nematode that affects small ruminants worldwide. While omics studies hold great promise, there are fewer research tools available for analyzing subsequent gene function studies. RNA interference (RNAi) technology offers a solution to this problem, as it especially allows for the knockout or shutting off of the expression of specific genes. As a result, RNAi technology has been widely used to explore gene function and disease treatment research. In this study, we reviewed the latest advancements in RNAi research on Haemonchus contortus in China, with the aim of providing a reference for the identification of key genes involved in growth and development, anthelmintic resistance, diagnostic markers, and diagnostic drug targets for the treatment of Haemonchus contortus.

Comparative structure activity and target exploration of 1,2-diphenylethynes in Haemonchus contortus and Caenorhabditis elegans

“…Possibly, orthogonal approaches, aimed at validating the protein targets identified here, could illuminate the genuine mode(s) of action of UMW-9729 in a nematode model. Complementary protein-focussed investigations, such as isothermal dose-response fingerprinting ( Jafari et al, 2014 ) or affinity-based assays ( Him et al, 2009 ; Seo and Corson, 2019 ), or genomics-directed studies, such as RNA interference ( Blanchard et al, 2018 ; Hou et al, 2023 ), CRISPR/Cas9 genome editing (cf. Waaijers et al, 2013 ; Quinzo et al, 2022 ) or resistance-based studies utilising either H. contortus (see Kaminsky et al, 2008 ) or C. elegans (see Burns et al, 2006 ), could be employed to identify and/or validate drug-protein interactions.…”

Structure-activity relationship and target investigation of 2-aryl quinolines with nematocidal activity

“…A genomics-focussed approach might also be utilised to identify and/or validate drug-protein interactions, through resistance-induction ( Burns et al, 2006 ; Kaminsky et al, 2008 ), RNA interference (RNAi; Ashrafi et al, 2003 ; Hou et al, 2023 ) or CRISPR/Cas9 technology ( Doudna and Charpentier, 2014 ). The identification of gene polymorphisms which confer drug resistance has been well-established in C. elegans (see Burns et al, 2006 ), and has been used to identify the targets of anthelmintics such as ivermectin ( Dent et al, 1997 ) and monepantel ( Kaminsky et al, 2008 ).…”

“…Although a laborious and time-consuming process, resistance has also been successfully induced in H. contortus via repeated drug dosing ( Kaminsky et al, 2008 ). Alternatively, RNAi-mediated gene knockdown has been performed in C. elegans (see Ashrafi et al, 2003 ), yet has been less successful in parasitic species such as H. contortus (reviewed by Hou et al, 2023 ). Another possible approach for target identification and/or validation would be the use of CRISPR/Cas9 genome engineering ( Doudna and Charpentier, 2014 ), whereby genes can be knocked-out or knocked-in.…”

RNAi-directed knockdown in the cnidarian fish blood parasite Sphaerospora molnari

“…However, using dsRNA in gene knockdown requires parameter optimization and evaluation regarding the target organism of use 11 . RNAi studies are demanding in non-model organisms that are difficult to cultivate in vitro, have complex life cycles, or are inappropriate for delivery methods for other reasons 12 – 14 . Among these, cnidarian parasites belonging to the Myxozoa represent a challenging model.…”