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Cholesterol-GalNAc Dual Conjugation Strategy for Reducing Renal Distribution of Antisense Oligonucleotides.
- Source :
-
Nucleic Acid Therapeutics . Feb2018, Vol. 28 Issue 1, p50-57. 8p. - Publication Year :
- 2018
-
Abstract
- Recently, some studies have reported nephrotoxicity associated with a certain class of antisense oligonucleotides (ASOs) in humans. One possibility for reducing the potential nephrotoxicity of ASOs is to alter their pharmacokinetics. In this study, we investigated the effect of a ligand conjugation strategy on the renal accumulation of ASOs. We selected two ligands, cholesterol and N-acetylgalactosamine (GalNAc), with the purpose of reducing renal distribution and liver targeting, and then designed a series of cholesterol-GalNAc dual conjugated ASOs. The gene-silencing activity of the cholesterol-GalNAc dual conjugated ASO in the liver was slightly lower than that of a GalNAc-conjugated ASO. On the other hand, the renal distribution of the cholesterol-GalNAc dual conjugated ASO was considerably decreased compared with the GalNAc-conjugated ASO, as we expected. As dual conjugation was successful in reducing the renal distribution of ASO, it should be an effective strategy for reducing the nephrotoxic potential of ASOs. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 21593337
- Volume :
- 28
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Nucleic Acid Therapeutics
- Publication Type :
- Academic Journal
- Accession number :
- 127615202
- Full Text :
- https://doi.org/10.1089/nat.2017.0698