ANTISENSE OLIGONUCLEIC ACID
FIG15 is a graph showing the results of hepatotoxicity of antisense oligonucleic acid evaluated in the Example described later
In the same manner as in the above-mentioned Example 1 except that #101 or a derivative thereof #101-G4-6 was used, hepatotoxicity was evaluated. The theoretical value of the molecular weight of #101-G4-6 was 4668.61 and the measured value was 4670.31. The sequence of each antisense oligonucleic acid used in this Example is shown in Table 15, and the measurement results of the hepatotoxicity are shown in FIG15. In FIG15, "*" indicates presence of a significant difference at p<0.05.[Table 15]#101G T T a t g c c a c c mC T A#101-G4-6G T T a t µ c c a c c mC T A As shown in the results of FIG15, the serum concentrations of AST and ALT could be reduced by only converting guanine, which is in one of the 2',4'-non-bridged nucleic acid residues in the middle part of antisense oligonucleic acid #101 having very high hepatotoxicity, to 8-bromoguanine.
graph
15
solution
100
than
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."]