ANTISENSE OLIGONUCLEIC ACID
FIG1 is a graph showing the results of hepatotoxicity of antisense oligonucleic acid evaluated in the Example described later
Five-week-old male C57BL/6NCrl mice (Nihon Charles River Co., Ltd.) were quarantined and acclimated for 1 week and used for experiments. The mice were optionally divided into 3 groups (4 mice per group), and physiological saline (manufactured by Otsuka Pharmaceutical Co., Ltd.) or each antisense oligonucleic acid solution was administered once at a dose of 10 mL/kg body weight (20 mg/kg body weight as dose of antisense oligonucleic acid) from the tail vein. On the fourth day (96 hours later), the mice were anesthetized by inhalation of 2.0 to 4.0% isoflurane (manufactured by DS Pharma Animal Health), and blood was collected from the abdominal portion of posterior vena cava as much as possible. The obtained blood was allowed to stand at room temperature for 20 to 60 min and centrifuged at 1700xg for 5 min to give serum. At the time of blood collection, when the blood volume did not reach the amount necessary for analysis, it was diluted with water for injection and used for the analysis. The concentrations of aspartate transaminase (AST) and alanine transaminase (ALT) in the obtained serum were measured using an automatic biochemical analyzer ("JCA-BM6070" manufactured by JEOL Ltd.). The breeding and experiment of the above-mentioned animal experiment were conducted in the animal experiment facility of Safety Laboratory, SHIN NIPPON BIOMEDICAL LABORATORIES, LTD. in accordance with the animal experiment regulations of SHIN NIPPON BIOMEDICAL LABORATORIES, LTD. The results are shown in FIG1. In FIG1, "*" indicates presence of a significant difference at p<0.05. As shown in the results of FIG1, AST and ALT are enzymes to be the indices of liver dysfunction, and the serum concentrations of these enzymes due to particularly high hepatotoxicity of #101 could be reduced significantly only by changing cytosine, which is in one of the 2',4'-non-bridged nucleic acid residues in the middle part, to 5-hydroxycytosine.
graph
100
than
10
than
1
Example
["1. An antisense oligonucleic acid having a base length of not less than 7nt and not more than 30nt, wherein nucleic acid residues of not less than 1nt and not more than 5nt respectively from the both terminals are 2',4'-bridged nucleic acids, 2',4'-non-bridged nucleic acid residue(s) is(are) present between the both terminals, and one or more bases in the nucleic acid residue(s) of the 2',4'-non-bridged nucleic acid residue(s) is/are modified."]