ANTISENSE OLIGONUCLEIC ACID
FIG17 is a graph showing the results of hepatotoxicity of antisense oligonucleic acid and GR gene expression-suppressing activity evaluated in the Example described later
With regard to each of the obtained antisense oligonucleic acids, the ALT concentration in mouse serum and GR gene expression-suppressing activity were measured in the same manner as in the above-mentioned Example 3. The results are shown in FIG17. In FIG17, "*" indicates presence of a significant difference at p<0.05. As shown in the results of FIG17 (1), the hepatotoxicity by Posi14 was reduced to 30% by only changing guanine, which is in one of the 2',4'-non-bridged nucleic acid residues in the middle part, to 8-bromoguanine. On the other hand, as shown in the results of FIG17 (2), GR gene expression-suppressing activity almost did not change even when guanine, which is in one of the 2',4'-non-bridged nucleic acid residues in the middle part of Posi14, was changed to 8-bromoguanine. Thus, according to the present invention, hepatotoxicity can be reduced without reducing the activity of antisense oligonucleic acid.
graph
100
than
17
sequence shown in Table
10
than
["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."]