Treatment of atonal homolog 1 (ATOH1) related diseases by inhibition of natural antisense transcript to ATOH1
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of Atonal homolog 1 (ATOH1), in particular, by targeting natural antisense polynucleotides of Atonal homolog 1 (ATOH1). The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of ATOH1.
1. A method of upregulating a function of and/or the expression of an Atonal homolog 1 (ATOH1) polynucleotide having SEQ ID NO: 1 in mammalian cells or tissues in vivo or in vitro comprising: contacting said cells or tissues with at least one short interfering RNA (siRNA) oligonucleotide 19 to 30 nucleotides in length, said at least one siRNA oligonucleotide being at least 95% complementary to and specific for a natural antisense polynucleotide of an Atonal homolog 1 (ATOH1) polynucleotide having SEQ ID NO: 2 and, wherein said siRNA oligonucleotide upregulates a function of and/or the expression of Atonal homolog 1 (ATOH1) gene in mammalian cells or tissues in vivo or in vitro.
2. The method of claim 1 , wherein said oligonucleotide has 100% sequence complementarity to a sequence of at least about 19 consecutive nucleic acids on a natural antisense polynucleotide of the Atonal homolog 1 (ATOH1) polynucleotide having SEQ ID NO: 2.
3. The method according to claim 2 wherein the at least one siRNA specifically hybridizes to a non-overlapping region of said natural antisense polynucleotide wherein said non-overlapping region is non-overlapping with the mRNA of said ATOH1 gene.
4. The method of claim 3 wherein the function or expression of said ATOH1 gene is increased relative to a mock-transfected control.
5. The method of claim 1 wherein the siRNA is 19-27 nucleotides in length.
6. The method according to claim 5 wherein the siRNA has a sequence selected from SEQ ID NO: 3 or 4.