tetano
Editor, Senior Moderator
Nat Commun
. 2026 Aug 26;17(1):9052.
doi: 10.1038/s41467-026-76465-9.
Wannaporn Ittiprasert 1 , Michael J Smout 2 3 , Victoria H Mann 1 , Matthew Moyle 2 , Sean M Kinahan 4 5 , Daniel N Ackerman 4 5 , Danielle N Rivera 4 5 , Joshua L Santarpia 4 5 , Eric C Carnes 5 6 , Margaret M Mentink-Kane 7 , Marina Reis Costa 1 , Cornelis H Hokke 8 , Meta Roestenberg 8 , Maria Elena Bottazzi 9 10 , Bethany K Bracken 11 , Bruce A Rosa 12 , Sergej Djuranovic 13 14 15 , Darren A Pickering 2 , Paul R Giacomin 2 , Daniel Watterson 16 17 , Naphak Modhiran 16 17 , Max F Moescheid 18 , Christoph G Grevelding 18 , Makedonka Mitreva 12 19 20 , Alex Loukas 21 22 , Paul J Brindley 23
Affiliations
We report the generation and propagation of not only the first heritable transgenic schistosome line but also a line that secretes a functional therapeutic protein in vivo. Using multiplexed CRISPR/Cas-mediated homology-directed knock-in targeted to a predicted genomic safe-harbor, we inserted a VHH-IgG1 Fc (termed C5-Fc) transgene into Schistosoma mansoni eggs. Single-miracidium infections of Biomphalaria glabrata yielded parental P0 lines; serial passage through snail and mouse hosts produced an F2 cohort in which all parasites carried the C5-Fc transgene and secreted C5-Fc into the murine venous circulation. Molecular assays confirmed chromosomal insertion, germline transmission and systemic secretion. Sera from mice harboring C5-Fc transgenic worms neutralized SARS-CoV-2 in vitro with potent activity consistent with the expected ACE2-binding blockade by the C5 variable domain of heavy-chain-only antibody (VHH). These results demonstrate (i) stable, heritable transgenesis of a platyhelminth, (ii) delivery of a biologically active antibody fragment by a live helminth in a mammalian host, and (iii) feasibility of using transgenic schistosomes as sustained, single-dose protein delivery platforms. This technology and delivery system enable new experimental approaches for schistosome biology and motivate exploration of living-foundry therapeutics.
. 2026 Aug 26;17(1):9052.
doi: 10.1038/s41467-026-76465-9.
Heritable transgenic schistosomes as a living platform for SARS-CoV-2 neutralizing antibody secretion
Wannaporn Ittiprasert 1 , Michael J Smout 2 3 , Victoria H Mann 1 , Matthew Moyle 2 , Sean M Kinahan 4 5 , Daniel N Ackerman 4 5 , Danielle N Rivera 4 5 , Joshua L Santarpia 4 5 , Eric C Carnes 5 6 , Margaret M Mentink-Kane 7 , Marina Reis Costa 1 , Cornelis H Hokke 8 , Meta Roestenberg 8 , Maria Elena Bottazzi 9 10 , Bethany K Bracken 11 , Bruce A Rosa 12 , Sergej Djuranovic 13 14 15 , Darren A Pickering 2 , Paul R Giacomin 2 , Daniel Watterson 16 17 , Naphak Modhiran 16 17 , Max F Moescheid 18 , Christoph G Grevelding 18 , Makedonka Mitreva 12 19 20 , Alex Loukas 21 22 , Paul J Brindley 23
Affiliations
- PMID: 42649193
- DOI: 10.1038/s41467-026-76465-9
Abstract
We report the generation and propagation of not only the first heritable transgenic schistosome line but also a line that secretes a functional therapeutic protein in vivo. Using multiplexed CRISPR/Cas-mediated homology-directed knock-in targeted to a predicted genomic safe-harbor, we inserted a VHH-IgG1 Fc (termed C5-Fc) transgene into Schistosoma mansoni eggs. Single-miracidium infections of Biomphalaria glabrata yielded parental P0 lines; serial passage through snail and mouse hosts produced an F2 cohort in which all parasites carried the C5-Fc transgene and secreted C5-Fc into the murine venous circulation. Molecular assays confirmed chromosomal insertion, germline transmission and systemic secretion. Sera from mice harboring C5-Fc transgenic worms neutralized SARS-CoV-2 in vitro with potent activity consistent with the expected ACE2-binding blockade by the C5 variable domain of heavy-chain-only antibody (VHH). These results demonstrate (i) stable, heritable transgenesis of a platyhelminth, (ii) delivery of a biologically active antibody fragment by a live helminth in a mammalian host, and (iii) feasibility of using transgenic schistosomes as sustained, single-dose protein delivery platforms. This technology and delivery system enable new experimental approaches for schistosome biology and motivate exploration of living-foundry therapeutics.