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

针对跨膜p24转运蛋白6和簇蛋白的RNA适体,可用于将成像试剂和RNA疗法靶向递送至人β细胞

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作者:Dimitri Van Simaeys #,Adriana De La Fuente #,Serena Zilio #,Alessia Zoso,Victoria Kuznetsova,Oscar Alcazar,Peter Buchwald,Andrea Grilli,Jimmy Caroli,Silvio Bicciato,Paolo Serafini

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.

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