Journal
BIOANALYSIS
Volume 11, Issue 21, Pages 1955-1965Publisher
Newlands Press Ltd
DOI: 10.4155/bio-2019-0118
Keywords
A-to-I editing; adenosine; deaminated metabolite; deamination; inosine; MS; metabolism; oligonucleotide; RNAi; small interfering RNA
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Aim: A novel single-stranded deaminated oligonucleotide metabolite resulting from a REVERSIR (TM) oligonucleotide was discovered and identified in monkey liver after subcutaneous administration. Results & methodology: REVERSIR-A and its metabolites were extracted from biological matrices by solid phase extraction and analyzed using LC coupled with high-resolution MS under negative ionization mode. A novel 9-mer metabolite of REVERSIR-A, resulting from deamination of the 3 ' terminal 2 ' -O-methyl-adenosine nucleotide to 2 ' -O-methyl-inosine, was discovered at significant levels in monkey liver. The metabolite's identity was confirmed by LC-MS/MS. Conclusion: This report describes the first observation of a long-chain deaminated metabolite of a single-stranded REVERSIR oligonucleotide in vivo in monkey liver.
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