The present invention relates to chemical modification motifs to be used for oligonucleotides. Oligonucleotides of the invention, such as the antisense oligonucleotides of chemical modification have increased in vivo efficacy. The oligonucleotides of chemical modification provides one or more effect of advantage, efficiency target specificity, toxicity, and/or the stability of delivering. The oligonucleotides of chemical modification has the lock nucleic acid (LNAs) of specific chemical modification motif or pattern. The oligonucleotides (for example) antisense oligonucleotides can be with target RNA, such as miRNA or mRNA. The method of composition and the oligonucleotides containing the chemical modification is also provided herein and is used as the various illnesss for the treatment of, including cardiovascular disease using the oligonucleotides of chemical modification.