Transgenesis in parasitic helminths: a brief history and prospects for the future

Abstract

Helminth infections impact the health of hundreds of millions of persons globally and also cause important economic losses in livestock farming. Methodological limitations as well as the low attention given to the study of helminths have impacted biological research and, thus, the procurement of accurate diagnosis and effective treatments. Understanding the biology of helminths using genomic and proteomic approaches could contribute to advances in understanding host–helminth interactions and lead to new vaccines, drugs and diagnostics. Despite the significant advances in genomics in the last decade, the lack of methodological adaptation of current transgenesis techniques has hampered the progression of post-genomic research in helminthology. However, the application of new techniques, such as CRISPR, to the study of trematodes and nematodes has opened new avenues for genome editing-powered functional genomics for these pathogens. This review summarises the historical advances in functional genomics in parasitic helminths and highlights pending limitations that will need to be overcome to deploy transgenesis tools. Graphical Abstract

Differential excretory/secretory proteome of the adult female and male stages of the human blood fluke,Schistosoma mansoni

“…Access by the field to transgenic schistosomes that (conditionally) secrete reporters, model antigens, and other informative gene products, along with advances in human challenge models (Langenberg et al, 2020) can be expected to lead to noteworthy progress in the immunobiology and pharmacology of these flukes (Hoffmann et al, 2014;Zamanian and Andersen, 2016;McVeigh and Maule, 2019;Douglas et al, 2021;Quinzo et al, 2022).…”

“…Moreover, identification of the most abundantly secreted proteins of both sexes enables future analysis of the regulatory elements and motifs that control the expression of the corresponding genes can assist with the development of transgenic schistosomes that over-express endogenous proteins, or even secrete foreign proteins. Access by the field to transgenic schistosomes that (conditionally) secrete reporters, model antigens, and other informative gene products, along with advances in human challenge models (Langenberg et al, 2020) can be expected to lead to noteworthy progress in the immunobiology and pharmacology of these flukes (Hoffmann et al, 2014;Zamanian and Andersen, 2016;McVeigh and Maule, 2019;Douglas et al, 2021;Quinzo et al, 2022).…”

Zoonotic Helminths and Their Influences on Humans

“…Consequently, some studies have dedicated effort on to transgenesis in these zoonotic helminths. Figure 5 shows historical milestones in the transgenesis of zoonotic helminths [1]. Nevertheless, current genome manipulation is still imperfect due to the specific complication of helminths' biology as well as their complex life process.…”

“…Over the years, helminths have been generally classified into 3 different groups, each of which consists of at least 50+ species scattering all over the world . In fact, parasitic helminths have infected approximately one sixth of the global population, posing significant healife cycle to both children and adults, and such large scale infections have induced roughly 14 million loss of the equivalent of one year of full health (DAYL) in 2000s [1]. Also, the roughly calculated helminth-infection-induced annual expense is roughly 2 billion USD in Europe alone [2].…”

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“…This will be of assistance in the development of transgenic schistosomes that over-express endogenous proteins, or even secrete foreign proteins. Access by the field to transgenic schistosomes that (conditionally) secrete reporters, model antigens, and other informative gene products, along with advances in human challenge models (Langenberg et al, 2020) can be expected to hasten progress in the immunobiology and pharmacology of these flukes (Hoffmann et al, 2014;Zamanian and Andersen, 2016;Mcveigh and Maule, 2019;Douglas et al, 2021;Quinzo et al, 2022).…”