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

Dimitri Van Simaeys, Adriana De La Fuente, Serena Zilio, Alessia Zoso, Victoria Kuznetsova, Oscar Alcazar, Peter Buchwald, Andrea Grilli, Jimmy Caroli, Silvio Bicciato and Paolo Serafini ()
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Dimitri Van Simaeys: University of Miami
Adriana De La Fuente: University of Miami
Serena Zilio: University of Miami
Alessia Zoso: University of Miami
Victoria Kuznetsova: University of Miami
Oscar Alcazar: University of Miami
Peter Buchwald: University of Miami
Andrea Grilli: University of Modena and Reggio Emilia
Jimmy Caroli: University of Modena and Reggio Emilia
Silvio Bicciato: University of Modena and Reggio Emilia
Paolo Serafini: University of Miami

Nature Communications, 2022, vol. 13, issue 1, 1-18

Abstract: Abstract 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.

Date: 2022
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29377-3

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DOI: 10.1038/s41467-022-29377-3

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