bis-cholesteryl-conjugated phosphorothioate oligodeoxynucleotides are highly selectively taken up by the liver
bis-cholesteryl-conjugated phosphorothioate oligodeoxynucleotides are highly selectively taken up by the liver
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DOI：
10.1124/jpet.302.2.619
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发表时间：
2002-08-01
影响因子：
3.5
通讯作者：
Van Berkel, TJC
中科院分区：
文献类型：
--
作者：
Bijsterbosch, MK;Manoharan, M;Van Berkel, TJC
我们以前通过结合单一胆固醇来调节血浆蛋白结合和肝细胞摄取硫代寡核苷酸(PS-ODN)。在这项研究中，我们研究了一种PS-ODN的生物学命运，命名为ISIS-9389(3‘，5’-双胆固醇连接的ISIS 3082)，提供了两个胆固醇基团。大鼠静脉注射[H-3]ISIS-9389后，[H-3]ISIS-9389从血浆中清除，半衰期为23.6±-0.3min。90分钟后(大约95%清除)，肝脏含有83.0+/-0.8%的剂量。与肝脏一起构成网状内皮系统的脾和骨髓分别占3.1+/-0.3和4.3+/-0.2%。所有其他组织堆积在一起
We previously modulated, by conjugating a single cholesterol, plasma protein binding and liver cell uptake of a phosphorothioate oligodeoxynucleotide (PS-ODN). In this study, we investigated the biological fate of a PS-ODN, denoted ISIS-9389 (3', 5'-bis-cholesteryl-conjugated ISIS 3082), provided with two cholesteryl moieties. After intravenous injection of into rats, [H-3]ISIS-9389 was cleared from plasma with a half-life of 23.6 +/- 0.3 min. After 90 min (approximately 95% cleared), the liver contained 83.0 +/- 0.8% of the dose. Spleen and bone (marrow), which constitute with the liver the reticuloendothelial system, contained 3.1 +/- 0.3 and 4.3 +/- 0.2%, respectively. All other tissues accumulated together