Treatment of sirtuin 1 (sirt1) related diseases by inhibition of natural antisense transcript to sirtuin 1
AssigneeOPKO CuRNA, LLC
InventorsJoseph Collard, Olga Khorkova Sherman, Carlos Coito, Belinda De Leon
Life of this patent
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Abstract
Oligonucleotide compounds modulate expression and/or function of Sirtuin 1 (SIRT1) polynucleotides and encoded products thereof. Methods for treating diseases associated with Sirtuin 1 (SIRT1) comprise administering one or more Oligonucleotide compounds designed to inhibit the SIRT1 natural antisense transcript to patients.
Claims34
A method of modulating function and/or expression of Sirtuin 1 (SIRT1) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with an antisense oligonucleotide 5 to 30 nucleotides in length wherein said oligonucleotide has at least 50% sequence identity to a reverse complement of polynucleotide comprising 5 to 30 consecutive nucleotides within nucleotides 1 to 1028 of SEQ ID NO:
- 2 or nucleotides 1 to 429 of SEQ ID NO:
- 3, or nucleotides 1 to 156 of SEQ ID NO:
- 4 or nucleotides 1 to 593 of SEQ ID NO:
- 5 (FIG. 11);
- thereby modulating function and/or expression of the Sirtuin 1 (SIRT1) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating function and/or expression of an Sirtuin 1 (SIRT1) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with an antisense oligonucleotide 5 to 30 nucleotides in length wherein said oligonucleotide has at least 50% sequence identity to a reverse complement of an antisense of the Sirtuin 1 (SIRT1) polynucleotide;
- thereby modulating function and/or expression of the Sirtuin 1 (SIRT1) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating function and/or expression of an Sirtuin 1 (SIRT1) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with an antisense oligonucleotide 5 to 30 nucleotides in length wherein said oligonucleotide has at least 50% sequence identity to an antisense oligonucleotide to an Sirtuin 1 (SIRT1) polynucleotide;
- thereby modulating function and/or expression of the Sirtuin 1 (SIRT1) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating function and/or expression of an Sirtuin 1 (SIRT1) polynucleotide in patient cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with an antisense oligonucleotide that targets a region of the natural antisense of a Sirtuin 1 (SIRT1) polynucleotide;
- thereby modulating function and/or expression of an Sirtuin 1 (SIRT1) polynucleotide in patient cells or tissues in vivo or in vitro.
A method of modulating an Sirtuin 1 (SIRT1) gene expression and/or function in mammalian cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with a short interfering RNA (siRNA) oligonucleotide 5 to 30 nucleotides in length specific for an antisense polynucleotide of an Sirtuin 1 (SIRT1) polynucleotide wherein said 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 Sirtuin 1 (SIRT1) polynucleotide;
- and, modulating an Sirtuin 1 (SIRT1) gene expression and/or function in mammalian cells or tissues in vivo or in vitro.
A method of modulating an Sirtuin 1 (SIRT1) gene expression and/or function in mammalian cells or tissues in vivo or in vitro comprising:
- contacting said cells or tissues with an 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 polynucleotide encoding an Sirtuin 1 (SIRT1) molecule wherein an antisense oligonucleotide has at least 50% sequence identity to at least one nucleic acid sequence set forth as SEQ ID NOs:
- 1 to 5;
- and, modulating an Sirtuin 1 (SIRT1) gene expression and/or function in mammalian cells or tissues in vivo or in vitro.
A synthetic, modified oligonucleotide comprising at least one modification wherein the modification comprises at least one internucleotide linkage of:
- alkylphosphonate, phosphorothioate, phosphorodithioate, alkylphosphonothioate, phosphoramidate, carbamate, carbonate, phosphate triester, acetamidate, carboxymethyl ester, or combinations thereof, wherein said oligonucleotide is an antisense compound which hybridizes to and modulates expression and/or function of Sirtuin 1 (SIRT1) molecules in vivo or in vitro as compared to a normal control.
A composition comprising one or more oligonucleotides specific for Sirtuin 1 (SIRT1) polynucleotides said polynucleotides comprising antisense sequences, complementary sequences, alleles, homologs, isoforms, variants, derivatives, mutants or fragments thereof.
A method of preventing or treating diseases associated with Sirtuin 1 (SIRT1) polynucleotides and/or encoded products thereof, comprising:
- administering to a patient a therapeutically effective dose of at least one antisense oligonucleotide that binds to a natural antiense sequence of Sirtuin 1 (SIRT1) polynucleotide and modulates expression of said Sirtuin 1 (SIRT1) polynucleotides;
- thereby preventing or treating diseases associated with Sirtuin 1 (SIRT1) polynucleotides and/or encoded products thereof.
A method of identifying and selecting oligonucleotides for in vivo administration comprising selecting a target polynucleotide associated with a disease state;
- identifying oligonucleotides comprising at least five consecutive nucleotides which are complementary to, or in an antisense orientation to the identified polynucleotide;
- and, measuring the thermal melting point between binding of the antisense oligonucleotide and target polynucleotide under stringent hybridization conditions;
- and, identifying and selecting oligonucleotides for in vivo administration.
Dependencies are inferred from the claim text.