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2014 ; 2
(4
): 509-512
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Tiny masking locked nucleic acids effectively bind to mRNA and inhibit binding of
microRNAs in relation to thermodynamic stability
#MMPMID24944797
Murakami K
; Miyagishi M
Biomed Rep
2014[Jul]; 2
(4
): 509-512
PMID24944797
show ga
MicroRNA (miRNA) therapeutics, whereby miRNA networks are modified to treat
disease, is attracting considerable attention in the field of nucleic acid
therapeutics. In this study, we described highly effective constructs of
miRNA-masking oligonucleotides (ONDs) that bind to mRNA and interfere with the
binding of miRNA to its target site. Moreover, the correlation between ONDs and
thermodynamics on the effect of masking mRNA was investigated. Using a reporter
system, we evaluated ONDs of various lengths that have been linked to O-methyl
groups and/or locked nucleic acids (LNAs) on their ability to inhibit binding of
miRNA to target mRNA in cultured cells. LNAs of 10-12 nucleotides (nt) exerted
the strongest inhibitory effects, which were similar to the inhibitory activity
of antisense ONDs against miRNA. No such inhibitory activity was observed with
the standard 22-nt O-methyl-modified RNA in the reporter system. The results of
melting temperature experiments combined with the masking activity that prevented
binding of miRNA to its target, suggested that a major contributor to the masking
activity in cells may be the thermodynamic properties of the complexes. Our
findings may contribute to the design of effective masking LNAs.