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Peer-reviewedCC BYScience Advances

Toward transgenic multicellular parasites: CRISPR-Cas12a germline editing of Schistosoma mansoni eggs as key to success

  • Max F. Moescheid1,2
  • Prapakorn Wisitpongpun2,3
  • Vanessa Gross1
  • Victoria H. Mann2
  • Thomas Quack1
  • Anne Rognon4
  • Christoph Grunau4
  • Wannaporn Ittiprasert2
  • Paul J. Brindley2
  • Christoph G. Grevelding1
4 affiliations
  1. 1Institute of Parasitology, Biomedical Research Center Seltersberg (BFS), Justus Liebig University Giessen, Germany.
  2. 2Department of Microbiology, Immunology & Tropical Medicine, School of Medicine & Health Sciences, George Washington University, Washington, DC 20037, USA.
  3. 3Cellular and Molecular Immunology Research Unit (CMIRU), Faculty of Allied Health Sciences, Naresuan University, Phitsanulok 65000, Thailand.
  4. 4IHPE Univ Perpignan Via Domitia, CNRS, IFREMER, Univ Montpellier, Perpignan, France.
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Abstract

Lack of transgenesis methods impedes functional studies in platyhelminths. We present a substantially improved ribonucleic protein complex (RNP)–based genome editing approach for Schistosoma mansoni comparing Cas9 and Cas12a, the latter attained more efficient homology-directed insertion of a 5′-C6-PEG10–modified double-stranded donor template bearing 50-nucleotide microhomology arms into a genome safe-harbor site (GSH1). Electroporation of eggs recovered from host livers resulted in enhanced green fluorescent protein (EGFP) reporter activity, driven by an S. mansoni ubiquitin promoter and terminator. Hamster infection with transgenic cercariae, the infectious stage of this parasitic platyhelminth, recovered from miracidial infection of snails, or from sporocysts generated in vitro from transgenic miracidia and implantation in snails, produced EGFP-positive adult worms. Sequencing of the edited GSH1 and analyses of filial generations demonstrated chromosomal integration and the stable transformation of S. mansoni . Together, this approach advances schistosome transgenesis and may be pioneering for other platyhelminths, which lack functional genomics and transformation methods.

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Cite

BibTeXRIS
BibTeX
@article{moescheid2026toward,
  title = {{Toward transgenic multicellular parasites: CRISPR-Cas12a germline editing of Schistosoma mansoni eggs as key to success}},
  author = {Max F. Moescheid and Prapakorn Wisitpongpun and Vanessa Gross and Victoria H. Mann and Thomas Quack and Anne Rognon and Christoph Grunau and Wannaporn Ittiprasert and Paul J. Brindley and Christoph G. Grevelding},
  journal = {Science Advances},
  year = {2026},
  month = oct,
  doi = {10.1126/sciadv.aeh0455},
  url = {https://www.science.org/doi/10.1126/sciadv.aeh0455},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Toward transgenic multicellular parasites: CRISPR-Cas12a germline editing of Schistosoma mansoni eggs as key to success
AU  - Max F. Moescheid
AU  - Prapakorn Wisitpongpun
AU  - Vanessa Gross
AU  - Victoria H. Mann
AU  - Thomas Quack
AU  - Anne Rognon
AU  - Christoph Grunau
AU  - Wannaporn Ittiprasert
AU  - Paul J. Brindley
AU  - Christoph G. Grevelding
PY  - 2026
DA  - 2026/10/02
JO  - Science Advances
DO  - 10.1126/sciadv.aeh0455
UR  - https://www.science.org/doi/10.1126/sciadv.aeh0455
AB  - Lack of transgenesis methods impedes functional studies in platyhelminths. We present a substantially improved ribonucleic protein complex (RNP)–based genome editing approach for Schistosoma mansoni comparing Cas9 and Cas12a, the latter attained more efficient homology-directed insertion of a 5′-C6-PEG10–modified double-stranded donor template bearing 50-nucleotide microhomology arms into a genome safe-harbor site (GSH1). Electroporation of eggs recovered from host livers resulted in enhanced green fluorescent protein (EGFP) reporter activity, driven by an S. mansoni ubiquitin promoter and terminator. Hamster infection with transgenic cercariae, the infectious stage of this parasitic platyhelminth, recovered from miracidial infection of snails, or from sporocysts generated in vitro from transgenic miracidia and implantation in snails, produced EGFP-positive adult worms. Sequencing of the edited GSH1 and analyses of filial generations demonstrated chromosomal integration and the stable transformation of S. mansoni . Together, this approach advances schistosome transgenesis and may be pioneering for other platyhelminths, which lack functional genomics and transformation methods.
SN  - 2375-2548
ER  -