ANTISENSE OLIGONUCLEIC ACID
FIG16 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 #12, #98, #14 or derivatives thereof were used instead of antisense oligonucleic acid #101, hepatotoxicity was evaluated. The theoretical value of the molecular weight of #12-G4-9 was 4693.62 and the measured value was 4692.50, the theoretical value of the molecular weight of #98-G4-6 was 4692.64 and the measured value was 4693.45, the theoretical value of the molecular weight of #14-G4-5 was 4685.60 and the measured value was 4683.86. The sequence of each antisense oligonucleic acid used in this Example is shown in Table 16, and the measurement results of the hepatotoxicity are shown in FIG16. In FIG16, "*" indicates presence of a significant difference at p<0.05.[Table 16]#12G T mC c g c a t g c c T A A#12-G4-9G T mC c g c a t µ c c T A A#98G A T a t g c c c t a mC T A#98-G4-6G A T a t µ c c c t a mC T A#14G T A t g c c t c c g T T A#14-G4-5G T A t µ c c t c c g T T A As shown in the results of FIG16, the serum concentratio ns of AST and ALT could be reduced significantly only by changin g guanine, which is in one of the 2',4'-non-bridged nucleic acid residues in the middle part, to 8-bromoguanine also in other an tisense oligonucleic acids #12, #98 and #14 having high hepatoto xicity.
graph
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16
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["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."]