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Organ distribution and stability of phosphorothioated oligodeoxyribonucleotides in mice
Author(s) -
Goodarzi Goodarz,
Watabe Misako,
Watabe Kounosuke
Publication year - 1992
Publication title -
biopharmaceutics and drug disposition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.419
H-Index - 58
eISSN - 1099-081X
pISSN - 0142-2782
DOI - 10.1002/bdd.2510130308
Subject(s) - toxicity , distribution (mathematics) , pharmacology , ratón , nucleotide , chemistry , medicine , biochemistry , mathematical analysis , mathematics , gene
Results of recent studies in our laboratory have suggested a potential role for antisense oligodeoxyribonucleotides (oligo(dN)s) as therapeutic agents in the treatment of human hepatitis B virus infection. As a first step towards assessing the potential utility of oligo(dN) in therapy, we have examined the organ distribution, stability and toxicity of a phosphorothioated oligo(dN) (S‐oligo) of 20 nucleotides in length which was administered to mice via different routes. Among the various organs analysed, the liver retained the highest amount of S‐oligo (1·3–2 per cent of the total injection) at the peak time (10–30 min) regardless of the route of injection. However, the S‐oligo appeared to be degraded in the liver to about 40 per cent of its original length within 30 min of injection, presumably by the action of 3′ exonucleases. Injection of doses of up to 5 mg kg −1 of S‐oligo had no apparent toxic effects on the mice.