Micro-RNA scaffolds and non-naturally occurring micro-RNAs

A method of delivery of a mature endogenous miRNA to a cell, the method comprising:

• introducing in said cell a non-naturally occurring miR-196a-2 miRNA, wherein said non-naturally occurring miR-196a-2 miRNA comprises a nucleic acid having a stem-loop structure, wherein the stem of the stem-loop structure incorporates a miRNA-196-a-2 scaffold, and a mature strand-star strand duplex, wherein said mature strand has a sequence derived from a mature endogenous miRNA, wherein said mature endogenous miRNA has a sequence that is distinct from the sequence of the endogenous mature strand of miR-196a-2, wherein position 1 of the mature strand is U and the opposite nucleotide in the star strand is G and the duplex contains a mismatch at position 12 of the mature strand and either no additional mismatches or wobble pairs at any position other than positions 1 and 12 of the mature strand, or mismatches or wobble pairs at one or more of positions other than at positions 2, 3, 4, 6, 7, 8, 9, 10, 11, 13, 14, 15, 16 and 17 within the duplex, wherein positions of the mature strand are numbered relative to the 5′ end of the mature strand, and the mature strand is about 19-25 nucleotides in length;
• wherein said non-naturally occurring miR-196a-2 miRNA is processed in said cell to yield a mature miRNA having the sequence of said mature strand.