Regular ArticleA Nonradioisotope Biomedical Assay for Intact Oligonucleotide and Its Chain-Shortened Metabolites Used for Determination of Exposure and Elimination Half-Life of Antisense Drugs in Tissue
References (27)
- et al.
J. Biol. Chem.
(1994) - et al.
Biochem. Pharmacol.
(1997) - et al.
Kidney Int.
(1995) - et al.
Anal. Biochem.
(1996) - et al.
Bioorg. Med. Chem. Lett.
(1997) - et al.
Bioorg. Med. Chem. Lett.
(1994) - et al.
Kidney Int.
(1995) - et al.
Mol. Pharmacol.
(1996) - et al.
Mol. Carcinogen.
(1997) Proceedings, X111th International Congress of Pharmacology
(1998)
J. Pharmacol. Exp. Ther.
J. Pharmacol. Exp. Ther.
Proc. Natl. Acad. Sci. USA
Cited by (30)
Assessment of the Drug Interaction Potential of Unconjugated and GalNAc<inf>3</inf>-Conjugated 2′-MOE-ASOs
2017, Molecular Therapy Nucleic AcidsElucidation of the Biotransformation Pathways of a Galnac<inf>3</inf>-conjugated Antisense Oligonucleotide in Rats and Monkeys
2016, Molecular Therapy Nucleic AcidsCitation Excerpt :In light of these observations, and based on internal data, previous animal studies revealed that GalNAc sugars and the trishexylamino (THA) cluster were rapidly cleaved within minutes to hours from GalNAc-conjugated ASOs following subcutaneous (SC) administrations, releasing unconjugated ASOs in liver to exhibit their pharmacological effects. It is well understood that unconjugated ASOs are slowly metabolized to chain-shortened oligonucleotide metabolites by nucleases and eliminated in urine.9 Hence, the distribution, metabolism, and fate of unconjugated ASOs are well established, yet the metabolic pathway of the THA cluster containing GalNAc3 as a targeting moiety has never been reported and is important to help understand the efficacy and safety of the conjugated ASO.
Renal uptake and tolerability of a 2'-O-methoxyethyl modified antisense oligonucleotide (ISIS 113715) in monkey
2012, ToxicologyCitation Excerpt :Representative samples of both kidneys were stained with hematoxylin and eosin and processed from all animals for microscopic examination. Tissue samples were analyzed using a validated capillary gel electrophoresis (CGE) method (Geary et al., 1999). The linear calibration range of the assay was 0.15–20 μM (1.14–151 μg/g for parent compound), with the low end of this range defining the lower limit of quantitation (LLOQ).
A combined solid phase extraction/capillary gel electrophoresis method for the determination of phosphorothioate oligodeoxynucleotides in biological fluids, tissues and feces
2009, Journal of Chromatography B: Analytical Technologies in the Biomedical and Life SciencesBiodistribution and metabolism of immunostimulatory oligodeoxynucleotide CPG 7909 in mouse and rat tissues following subcutaneous administration
2005, Biochemical PharmacologyCitation Excerpt :Liver and kidney showed a much higher percentage of metabolites than injection site and local lymph nodes, where 3′-exonuclease activity as well as endonuclease activity appeared to be lower. This may be due to different organ distribution of degrading enzymes [29] rather than a reflection of differences in the disposition properties of the individual metabolites. We have no indication for differential distribution pathways for different metabolites.