Nature communications · 2026
Heritable transgenic schistosomes as a living platform for SARS-CoV-2 neutralizing antibody secretion.
СтатьяПоддержка NIH: внешняя программаПоддержка правительства СШАПоддержка исследования: вне правительства СШАНазвание и аннотация: Перевод в очереди
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Ittiprasert Wannaporn, Smout Michael J, Mann Victoria H, Moyle Matthew, Kinahan Sean M, Ackerman Daniel N, Rivera Danielle N, Santarpia Joshua L, Carnes Eric C, Mentink-Kane Margaret M, Costa Marina Reis, Hokke Cornelis H, Roestenberg Meta, Bottazzi Maria Elena, Bracken Bethany K, Rosa Bruce A, Djuranovic Sergej, Pickering Darren A, Giacomin Paul R, Watterson Daniel, Modhiran Naphak, Moescheid Max F, Grevelding Christoph G, Mitreva Makedonka, Loukas Alex, Brindley Paul J
Аннотация
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.