Modulating Anti-MicroRNA-21 Activity and Specificity Using Oligonucleotide Derivatives and Length Optimization

Table 1

Oligonucleotides used in this study.The anti-miR21 ONs used in this study, ranging from 9 to 22 nucleotides in length. The ONs are 2′OMe RNA, LNA/2′OMe RNA mixmers with or without phosphorothioate backbone, and LNA/2′OMe/UNA mixmers. Corresponding ONs with 2MMs were synthesized. Mismatched bases are mismatched against the bases 9 and 11 in the target miR21 sequence. Phosphorothioate AMOs are denoted with PS, ONs lacking this denotation are phosphodiester AMOs. Capital letters represent 2′OMe ribonucleotides. Lowercase letters indicate LNA monomers, whereas underlined letters represent UNA monomers. Italic letters mark mismatches and bold letters phosphorothioates.

Sequence	Name	Chemistry	Mismatches	LNA-mismatches
3′- AGU UGU AGU CAG ACU AUU CGA U-5′	Original miR21 sequence		0	0
5′-UCA ACA UCA GUC UGA UAA GCU A-3′	22AMO	0% LNA	0	0
5′-UCA ACA UCU GAC UGA UAA GCU A-3′	22AMO_2MM	0% LNA	2	0
5′- UcA aCa UcA gUc UgA uAa GcU a-3′	22AMO_50%	50% LNA	0	0
5′- UcA aCa UcU gAc UgA uAa GcU a-3′	22AMO_50%_2MM	50% LNA	2	0
5′- UcA AcA UcA GuC UgA UaA GcU A-3′	22AMO_32%	32% LNA	0	0
5′- UcA AcA UcU GaC UgA UaA GcU A-3′	22AMO_32%_2MM	32% LNA	2	1
5′- UcA AcA UcA GuC UgA UaA GcU A-3′	22AMO_32%_PS	PS 32% LNA	0	0
5′- UcA AcA UcU GaC UgA UaA GcU A-3′	22AMO_32%_2MM_PS	PS 32% LNA	2	1
5′- AcA UcA GuC UgA UaA GcU -3′	18AMO_33%	33% LNA	0	0
5′- AcA UcU GaC UgA UaA GcU -3′	18AMO_33%_2MM	33% LNA	2	1
5′- AcA UcA GuC UgA UaA -3′	15AMO_33%	33% LNA	0	0
5′- AcA UcU GaC UgA UaA -3′	15AMO_33%_2MM	33% LNA	2	1
5′- AcA UcA GuC UgA -3′	12AMO_33%	33% LNA	0	0
5′- AcA UcU GaC UgA -3′	12AMO_33%_2MM	33% LNA	2	1
5′- UcA GuC UgA -3′	9AMO_33%	33% LNA	0	0
5′- UcU GaC UgA -3′	9AMO_33%_2MM	33% LNA	2	1
5′-UcA  AcA  UcA  GuC  UgA  UaA  GcU  A-3′	22AMO_68%_PS	PS 68% LNA,32%UNA	0	0
5′-UcA  AcA  UcU  G a C   UgA  UaA  GcU  A-3′	22AMO_68%_2MM_PS	PS 68% LNA,32%UNA	2	1
5′- uCa aca uCa guc uGa uaa gCu a-3′	22AMO_68%_PS	PS 68% LNA,18%UNA	0	0
5′- uCa aca uC u gAc uGa uaa gCu a-3′	22AMO_68%_2MM_PS	PS 68% LNA,18%UNA	2	1