RNA aptamers specific for transmembrane p24 trafficking protein 6 and Clusterin for the targeted delivery of imaging reagents and RNA therapeutics to human β cells

Nat Commun. 2022 Apr 5;13(1):1815. doi: 10.1038/s41467-022-29377-3.


The ability to detect and target β cells in vivo can substantially refine how diabetes is studied and treated. However, the lack of specific probes still hampers a precise characterization of human β cell mass and the delivery of therapeutics in clinical settings. Here, we report the identification of two RNA aptamers that specifically and selectively recognize mouse and human β cells. The putative targets of the two aptamers are transmembrane p24 trafficking protein 6 (TMED6) and clusterin (CLUS). When given systemically in immune deficient mice, these aptamers recognize the human islet graft producing a fluorescent signal proportional to the number of human islets transplanted. These aptamers cross-react with endogenous mouse β cells and allow monitoring the rejection of mouse islet allografts. Finally, once conjugated to saRNA specific for X-linked inhibitor of apoptosis (XIAP), they can efficiently transfect non-dissociated human islets, prevent early graft loss, and improve the efficacy of human islet transplantation in immunodeficient in mice.

MeSH terms

  • Animals
  • Aptamers, Nucleotide* / genetics
  • Clusterin* / genetics
  • Graft Rejection
  • Humans
  • Indicators and Reagents
  • Islets of Langerhans Transplantation*
  • Islets of Langerhans* / metabolism
  • Mice
  • RNA / metabolism
  • Vesicular Transport Proteins* / genetics


  • Aptamers, Nucleotide
  • Clusterin
  • Indicators and Reagents
  • TMED6 protein, mouse
  • Vesicular Transport Proteins
  • RNA