Methods and compositions for selecting siRNA of improved functionality
Efficient sequence specific gene silencing is possible through the use of siRNA technology. By selecting particular siRNAs by rational design, one can maximize the generation of an effective gene silencing reagent, as well as methods for silencing genes. Methods, compositions, and kits generated through rational design of siRNAs are disclosed including those directed to nucleotide sequences for TTR.
1. An siRNA molecule, wherein said siRNA molecule consists of: (a) a duplex region; and
(b) either no overhang regions or at least one overhang region, wherein each overhang region contains six or fewer nucleotides, wherein the duplex region consists of a sense region and an antisense region, wherein said sense region and said antisense region together form said duplex region and said sense region and said antisense region are each 19-30 nucleotides in length and said antisense region comprises a sequence that is the complement of SEQ ID NO:463.
2. The siRNA molecule of claim 1 , wherein said antisense region and said sense region are each 19-25 nucleotides in length.
3. The siRNA molecule of claim 2 , wherein said antisense region and said sense region are each 19 nucleotides in length.
4. The siRNA molecule of claim 1 , wherein said siRNA molecule has at least one overhang region.
5. The siRNA molecule of claim 1 , wherein said siRNA molecule has no overhang regions.
6. The siRNA molecule of claim 2 , wherein said siRNA molecule has at least one overhang region.
7. The siRNA molecule of claim 2 , wherein said siRNA molecule has no overhang regions.
8. The siRNA molecule of claim 3 , wherein said siRNA molecule has at least one overhang region.
9. The siRNA molecule of claim 3 , wherein said siRNA molecule has no overhang regions.
10. A chemically synthesized double stranded siRNA molecule, wherein:
(a) each strand of said double stranded siRNA molecule is between 19 and 30 nucleotides in length; and
(b) one strand of said siRNA molecule comprises a sequence that is the complement of SEQ ID NO:463.
11. The chemically synthesized double stranded siRNA molecule of claim 10 , wherein each strand of said siRNA molecule is 19-25 nucleotides in length.
12. The chemically synthesized double stranded siRNA molecule of claim 11 , wherein each strand of said siRNA molecule is 19 nucleotides in length.