Methods of inducing insulin production
The present invention provides a method of inducing insulin production in a cell by up-regulating a target gene involved in insulin production in said cell using an saRNA (short activating ribonucleic acid) which specifically down-regulates a target antisense RNA transcript present in said cell, wherein (i) said target RNA transcript is complementary to a sequence located on the coding strand of the target gene between 1000 nucleotides upstream and 1000 nucleotides downstream of the transcription start site of the target gene; and (ii) said sRNA is a single or double stranded RNA molecule up to 30 nucleotides in length comprising a sequence of at least 13 nucleotides which has at least 95% complementarity to a region of the target transcript. Also provided are certain saRNA molecules and uses thereof, particular medical uses, and induced cells and uses thereof.
1. A short activating ribonucleic acid (saRNA) which upregulates PDX1 expression in a cell, said saRNA having a first strand consisting of (i) a sequence selected from SEQ ID NO: 15, 16, 17, and 18; and (ii) a 3′ tail formed of 1-5 uracils.
2. An saRNA according to claim 1 , wherein said 3′ tail is formed of 2 uracils.
3. A pharmaceutical composition comprising one or more saRNAs which upregulate PDX1 expression in a cell, selected from saRNAs having a first strand consisting of (i) a sequence selected from SEQ ID NO: 15, 16, 17 and 18; and (ii) a 3′ tail formed of 1-5 uracils.
4. A pharmaceutical composition according to claim 3 , wherein said 3′ tail of said saRNA is formed of 2 uracils.