Journal article

Targeting rapidly cycling receptors CD2 and CD7 increases nanoparticle delivery to primary CD4 T cells.

Paula M Cevaal, Abdalla Ali, Marcel Doerflinger, Christina Cortez-Jugo, Abigail Tan, Haiyin Liu, Moore Z Chen, Le Wang, Merle Dayton, Liana Mackiewicz, Stanislav Kan, Matthew Faria, Celine Gubser, René PM Lafleur, Robert De Rose, Angus PR Johnston, Frank Caruso, Michael Roche, Jori Symons, Sharon R Lewin

Nat Commun | Published : 2026

Open access

Abstract

T cells are critically important to many diseases but are traditionally difficult to transfect. We hypothesise that the delivery of therapeutic cargo to T cells can be improved by targeting nanoparticles to surface receptors that undergo rapid receptor-mediated endocytosis. Using an internalisation assay that labelled intracellular and surface proteins with different fluorophores, we find that CD2 and CD7 exhibit significantly higher internalisation than other T cell receptors, such as CD3 or CD4. Targeting CD2 and CD7 improves nanoparticle internalisation by non-stimulated, primary CD4+ T cells and enhances the specificity of association to CD4+ T cells. Similarly, functionalising mRNA-lipi..

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