The invention provides chemically modified oligonucleotides capable of inhibiting the expression (e.g., abundance) of miR-15 family miRNAs, including miR-15a, miR-15b, miR-16, miR-195, miR-424, and miR-497. The invention provides in some embodiments, oligonucleotides capable of inhibiting, in a specific fashion, the expression or abundance of each of miR-15a, miR-15b, miR-16, miR-195, miR-424, and miR-497. The invention further provides pharmaceutical compositions comprising the oligonucleotides, and methods of treating patients having conditions or disorders relating to or involving a miR-15 family miRNA, such as a cardiovascular condition. In various embodiments, the oligonucleotides provide advantages in one or more of potency, efficiency of delivery, target specificity, toxicity, and/or stability.本發明提供能夠抑制包括miR-15a、miR-15b、miR-16、miR-195、miR-424及miR-497在內之miR-15家族miRNA之表現(例如豐度)的化學修飾之寡核苷酸。在一些實施例中,本發明提供能夠以特異性方式抑制miR-15a、miR-15b、miR-16、miR-195、miR-424及miR-497中每一者之表現或豐度之寡核苷酸。本發明進一步提供包含該等寡核苷酸之醫藥組合物,及治療患有諸如心血管病狀的有關或涉及miR-15家族miRNA之病狀或病症之病患的方法。在各種實施例中,該等寡核苷酸在效力、遞送效率、靶特異性、毒性及/或穩定性中之一或多個方面提供益處。
