RNA molecules that upregulate insulin production
The present invention provides a short RNA capable of upregulating MafA expression in a human cell, wherein the short RNA includes a first strand which is 19 to 25 nucleotides in length and comprises the sequence AUCUGUACUGGAUGAGCGG (SEQ ID NO:1) or UUUCCCGCAGGAGAUUGAC (SEQ ID NO:2). Also provided are uses of the short RNA, particular medical uses, and induced cells and uses of the induced cells.
1. A RNA which consists of a first strand which is 19 to 24 nucleotides in length and (a) comprises the sequence AUCUGUACUGGAUGAGCGG (SEQ ID NO:1) or (b) comprises the sequence UUUCCCGCAGGAGAUUGAC (SEQ ID NO:2), and a second strand which is 19 to 24 nucleotides in length and which forms a duplex with SEQ ID NO: 1 or SEQ ID NO: 2, wherein 1-5 unpaired nucleotides are present at the 3′ end of SEQ ID NO: 1 or SEQ ID NO: 2 and at the 3′ end of said second strand, forming 3′ overhangs.
2. The RNA according to claim 1 , wherein each strand of said RNA has 1-3 unpaired nucleotides on its 3′ end.
3. An in vitro method of inducing production and secretion of insulin by a human islet cell, said method comprising contacting said cell with RNA which consists of a first strand which is 19 to 24 nucleotides in length and comprises the sequence UUUCCCGCAGGAGAUUGAC (SEQ ID NO:2), and a second strand which is 19 to 24 nucleotides in length and which forms a duplex with SEQ ID NO: 2, wherein 1-5 unpaired nucleotides are present at the 3′ end of SEQ ID NO: 2 and at the 3′ end of said second strand, forming 3′ overhangs.
4. The RNA as defined in claim 1 for use in therapy.
5. The RNA as defined in claim 1 for use in the treatment of diabetes, fatty liver or morbid obesity.
6. A pharmaceutical composition comprising one or more of the RNAs as defined in any one of claims 1 - 2 or ex vivo or in vitro human cell comprising one or more of said RNAs, or both, and a pharmaceutically acceptable diluant, carrier or excipient.
7. A kit comprising:
(i) a RNA Which consists of a first strand which is 19 to 24 nucleotides in length and comprises the sequence AUCUGUACUGGAUGAGCGG (SEQ ID NO:1) and wherein said RNA has a second strand which is 19 to 24 nucleotides in length and which forms a duplex with SEQ ID NO. 1, wherein 1-5 unpaired nucleotides are present on the 3′ end of SEQ ID NO: 1 and at the 3′ end of said second strand, forming a 3′ overhang; and
(ii) a RNA which consists of a first strand which is 19 to 24 nucleotides in length and comprises the sequence UUUCCCGCAGGAGAUUGAC (SEQ ID NO:2) and wherein said RNA has a second strand which is 19 to 24 nucleotides in length and which forms a duplex with SEQ ID NO. 2, wherein 1-5 unpaired nucleotides are present on the 3′ end of SEQ ID NO: 2 and at the 3′ end of said second strand, forming a 3′ overhang.