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- W1503749452 abstract "Oligodeoxynucleotides (ODNs) inhibit gene expression at various levels both in vitro and in vivo. In vivo, the efficacy of ODN-induced regulation of genes in specific cell types may be suboptimal owing to poor accumulation of ODNs in these cells. In addition, untimely elimination of ODNs through renal clearance, degradation, and scavenger receptor-mediated uptake may further impair their therapeutic activity. These hurdles can be at least partly overcome by targeted delivery of the ODNs to the desired site of action. As short (and in particular uncharged) oligothymidinylates are poor substrates for hepatic scavenger receptors that are responsible for the rapid elimination of ODNs by cells of the reticuloendothelial system, the results leave unanswered whether longer, charged, and miscellaneous ODN sequences can also be redirected to the aimed target cell in vivo. In this respect, it is crucial to analyze the tissue distribution and identify the cellular uptake sites within the liver, using full-length antisense sequences. In the study described in the chapter, in vivo evidence is provided that untimely elimination of a miscellaneous 20-mer ODN by the preceding scavenger pathways can be circumvented and, concomitantly, accumulation by parenchymal liver cells can be enhanced after derivatization with a small-sized synthetic galactoside with high affinity for the asialoglycoprotein receptor." @default.
- W1503749452 created "2016-06-24" @default.
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- W1503749452 date "2000-01-01" @default.
- W1503749452 modified "2023-09-26" @default.
- W1503749452 title "[23] Targeted delivery of antisense oligonucleotides to parenchymal liver cells in vivo" @default.
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- W1503749452 doi "https://doi.org/10.1016/s0076-6879(99)14113-2" @default.
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