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.

Autor: Van Simaeys, Dimitri, De La Fuente, Adriana, Zilio, Serena, Zoso, Alessia, Kuznetsova, Victoria, Alcazar, Oscar, Buchwald, Peter, Grilli, Andrea, Caroli, Jimmy, Bicciato, Silvio, Serafini, Paolo
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Zdroj: Nature Communications; 10/23/2022, Vol. 13 Issue 1, p1-18, 18p
Abstrakt: 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. Development of probes specific for human β-cells could aid in delivery of therapeutics and monitoring β-cells mass during diabetes progression or islet transplantation. Here the authors identify two RNA aptamers specific for β-cells that allow efficient transfection of human islets and β-cell quantification of human islet grafts in immunodeficient mice. [ABSTRACT FROM AUTHOR]
Databáze: Complementary Index
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