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.
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.
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针对跨膜p24转运蛋白6和Clusterin的RNA适体，用于靶向递送成像试剂和RNA疗法到人β细胞。
DOI：
10.1038/s41467-022-29377-3
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发表时间：
2022-04-05
影响因子：
16.6
通讯作者：
Serafini P
中科院分区：
文献类型：
--
作者：
Van Simaeys D;De La Fuente A;Zilio S;Zoso A;Kuznetsova V;Alcazar O;Buchwald P;Grilli A;Caroli J;Bicciato S;Serafini P
体内检测和靶向 β 细胞的能力可以大大改善糖尿病的研究和治疗方式。然而，缺乏特异性探针仍然阻碍了人类β细胞团的精确表征和临床环境中治疗的实施。在这里，我们报告了两种 RNA 适体的鉴定，它们特异性、选择性地识别小鼠和人类 β 细胞。两个适体的假定靶标是跨膜 p24 运输蛋白 6 (TMED6) 和簇蛋白 (CLUS)。当免疫缺陷小鼠全身给药时，这些适体识别人类胰岛移植物，产生与移植的人类胰岛数量成比例的荧光信号。这些适体与内源性小鼠 β 细胞发生交叉反应，并可监测小鼠胰岛同种异体移植物的排斥反应。最后，一旦与 X 连锁凋亡抑制剂 (XIAP) 特异性的 saRNA 结合，它们可以有效转染未解离的人胰岛，防止移植物早期丢失，并提高免疫缺陷小鼠中人胰岛移植的疗效。开发针对人类 β 细胞的特异性探针可以帮助在糖尿病进展或胰岛移植过程中提供治疗和监测 β 细胞质量。在这里，作者鉴定了两种 β 细胞特异性的 RNA 适体，可以有效转染人类胰岛，并对免疫缺陷小鼠体内的人类胰岛移植物进行 β 细胞定量。
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.
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影响因子：
12.3
作者：
Carpenter AE;Jones TR;Lamprecht MR;Clarke C;Kang IH;Friman O;Guertin DA;Chang JH;Lindquist RA;Moffat J;Golland P;Sabatini DM
通讯作者：
Sabatini DM
影响因子：
8.2
作者：
Cline, Gary W.;Naganawa, Mika;Calle, Roberto A.
通讯作者：
Calle, Roberto A.
影响因子：
10.3
作者：
Chayka, Olesya;Corvetta, Daisy;Sala, Arturo
通讯作者：
Sala, Arturo
DOI：
10.1080/20022727.2017.1341758
发表时间：
2017
期刊：
Nano reviews & experiments
影响因子：
--
作者：
Ito K;Ookawara S;Ishibashi K;Morishita Y
通讯作者：
Morishita Y
影响因子：
8.2
作者：
Cras-Méneur, C;Inoue, H;Permutt, MA
通讯作者：
Permutt, MA