A method of making an engineered RNA precursor comprising the steps of: (a) selecting a sequence of a messenger RNA (mRNA) of a target gene of a mammalian cell； and (b) engineering an RNA precursor comprising； i) a first stem portion comprising a sequence of about 18 to about 40 nucleotides that is substantially complementary to the selected mRNA sequence； ii) a second stem portion comprising a sequence of about 18 to about 40 nucleotides that is sufficiently complementary to the about 18 to about 40 nucleotide sequence of the first stem portion to hybridize with the first stem portion to form a duplex stem； and iii) a loop portion that connects the two stem portions, such that the engineered RNA precursor, when expressed in a cell, is processed by the cell to produce a duplex siRNA that mediates RNA interference (RNAi) by selectively cleaving the mRNA.
