Treatment of pancreatic developmental gene related diseases by inhibition of natural antisense transcript to a pancreatic developmental gene
First Claim
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1. A method of modulating a function of and/or the expression of a Pancreatic Developmental gene polynucleotide in patient cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with at least one antisense oligonucleotide 5 to 30 nucleotides in length wherein said at least one oligonucleotide has at least 50% sequence identity to a reverse complement of a polynucleotide comprising 5 to 30 consecutive nucleotides within nucleotides 1 to 1235 of SEQ ID SEQ ID NO;
6, 1 to 17,964 of SEQ ID NO;
7, 1 to 1 to 50,003 of SEQ ID SEQ ID NO;
8, 1 to 486 of SEQ ID NO;
9, 1 to 494 of SEQ ID NO;
10, 1 to 1992 of SEQ ID NO;
11, or 1 to 1767 of SEQ ID NO;
12;
thereby modulating a function of and/or the expression of the Pancreatic Developmental gene polynucleotide in patient cells or tissues in vivo or in vitro.
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Abstract
The present invention relates to antisense oligonucleotides that modulate the expression of and/or function of a Pancreatic Developmental gene, in particular, by targeting natural antisense polynucleotides of a Pancreatic Developmental gene. The invention also relates to the identification of these antisense oligonucleotides and their use in treating diseases and disorders associated with the expression of Pancreatic Developmental genes.
198 Citations
34 Claims
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1. A method of modulating a function of and/or the expression of a Pancreatic Developmental gene polynucleotide in patient cells or tissues in vivo or in vitro comprising:
contacting said cells or tissues with at least one antisense oligonucleotide 5 to 30 nucleotides in length wherein said at least one oligonucleotide has at least 50% sequence identity to a reverse complement of a polynucleotide comprising 5 to 30 consecutive nucleotides within nucleotides 1 to 1235 of SEQ ID SEQ ID NO;
6, 1 to 17,964 of SEQ ID NO;
7, 1 to 1 to 50,003 of SEQ ID SEQ ID NO;
8, 1 to 486 of SEQ ID NO;
9, 1 to 494 of SEQ ID NO;
10, 1 to 1992 of SEQ ID NO;
11, or 1 to 1767 of SEQ ID NO;
12;
thereby modulating a function of and/or the expression of the Pancreatic Developmental gene polynucleotide in patient cells or tissues in vivo or in vitro.- View Dependent Claims (13)
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2. A method of modulating a function of and/or the expression of a Pancreatic Developmental gene polynucleotide in patient cells or tissues in vivo or in vitro comprising:
contacting said cells or tissues with at least one antisense oligonucleotide 5 to 30 nucleotides in length wherein said as least one oligonucleotide has at least 50% sequence identity to a reverse complement of a natural antisense of a Pancreatic Developmental gene polynucleotide;
thereby modulating a function of and/or the expression of the Pancreatic Developmental gene polynucleotide in patient cells or tissues in vivo or in vitro.
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3. A method of modulating a function of and/or the expression of a Pancreatic Developmental gene polynucleotide in patient cells or tissues in vivo or in vitro comprising:
contacting said cells or tissues with at least one antisense oligonucleotide 5 to 30 nucleotides in length wherein said oligonucleotide has at least 50% sequence identity to an antisense oligonucleotide to the Pancreatic Developmental gene polynucleotide;
thereby modulating a function of and/or the expression of the Pancreatic Developmental gene polynucleotide in patient cells or tissues in vivo or in vitro.
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4. A method of modulating a function of and/or the expression of a Pancreatic Developmental gene polynucleotide in patient cells or tissues in vivo or in vitro comprising:
contacting said cells or tissues with at least one antisense oligonucleotide that targets a region of a natural antisense oligonucleotide of the Pancreatic Developmental gene polynucleotide;
thereby modulating a function of and/or the expression of the Pancreatic Developmental gene polynucleotide in patient cells or tissues in vivo or in vitro.- View Dependent Claims (5, 6, 7, 8, 9, 10, 11, 12)
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14. A method of modulating a function of and/or the expression of a Pancreatic Developmental gene 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 5 to 30 nucleotides in length, said at least one siRNA oligonucleotide being specific for an antisense polynucleotide of a Pancreatic Developmental gene polynucleotide, wherein said at least one siRNA oligonucleotide has at least 50% sequence identity to a complementary sequence of at least about five consecutive nucleic acids of the antisense and/or sense nucleic acid molecule of the Pancreatic Developmental gene polynucleotide; and
, modulating a function of and/or the expression of a Pancreatic Developmental gene in mammalian cells or tissues in vivo or in vitro.- View Dependent Claims (15)
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16. A method of modulating a function of and/or the expression of a Pancreatic Developmental gene in mammalian cells or tissues in vivo or in vitro comprising:
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contacting said cells or tissues with at least one antisense oligonucleotide of about 5 to 30 nucleotides in length specific for noncoding and/or coding sequences of a sense and/or natural antisense strand of a Pancreatic Developmental gene polynucleotide wherein said at least one antisense oligonucleotide has at least 50% sequence identity to at least one nucleic acid sequence set forth as SEQ ID NOS;
1 to 12; and
,modulating the function and/or expression of the Pancreatic Developmental gene in mammalian cells or tissues in vivo or in vitro.
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17. A synthetic, modified oligonucleotide of 10 to 22 nucleotidesin length comprising at least one modification wherein the at least one modification is selected from:
- at least one modified sugar moiety;
at least one modified internucleotide linkage;
at least one modified nucleotide, and combinations thereof;
wherein said oligonucleotide is an antisense compound which hybridizes to a natural antisenses polynucheotide of a Pancreatic gene and upregulates the function and/or expression of a Pancreatic Developmental gene in vivo or in vitro as compared to a normal control. - View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34)
- at least one modified sugar moiety;
Specification