Treatment of alpha-l-iduronidase (idua) related diseases by inhibition of natural antisense transcript to idua

A method of modulating a function of and/or the expression of an Alpha-L-Iduronidase (IDUA) 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 Alpha-L-Iduronidase (IDUA) polynucleotide;
• thereby modulating a function of and/or the expression of the Alpha-L-Iduronidase (IDUA) polynucleotide in patient cells or tissues in vivo or in vitro.

A method of modulating a function of and/or the expression of an Alpha-L-Iduronidase (IDUA) polynucleotide in a biological system comprising:

• contacting said system with at least one antisense oligonucleotide that targets a region of a natural antisense oligonucleotide of the Alpha-L-Iduronidase (IDUA) polynucleotide;
• thereby modulating a function of and/or the expression of the Alpha-L-Iduronidase (IDUA) polynucleotide.

A method of modulating a function of and/or the expression of an Alpha-L-Iduronidase (IDUA) 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 an Alpha-L-Iduronidase (IDUA) 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 Alpha-L-Iduronidase (IDUA) polynucleotide;
• and, modulating a function of and/or the expression of Alpha-L-Iduronidase (IDUA) in mammalian cells or tissues in vivo or in vitro.

A method of modulating a function of and/or the expression of Alpha-L-Iduronidase (IDUA) in mammalian cells or tissues in vivo or in vitro comprising:

• 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 an Alpha-L-Iduronidase (IDUA) 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 9;
• and, modulating the function and/or expression of the Alpha-L-Iduronidase (IDUA) in mammalian cells or tissues in vivo or in vitro.

A method of preventing or treating a disease associated with at least one Alpha-L-Iduronidase (IDUA) polynucleotide and/or at least one encoded product thereof, comprising:

• administering to a patient a therapeutically effective dose of at least one antisense oligonucleotide that binds to a natural antisense sequence of said at least one Alpha-L-Iduronidase (IDUA) polynucleotide and modulates expression of said at least one Alpha-L-Iduronidase (IDUA) polynucleotide;
• thereby preventing or treating the disease associated with the at least one Alpha-L-Iduronidase (IDUA) polynucleotide and/or at least one encoded product thereof.

A method of identifying and selecting at least one oligonucleotide selective for a natural antisense transcript of an IDUA gene as a selected target polynucleotide for in vivo administration comprising:

• identifying at least one oligonucleotide comprising at least five consecutive nucleotides which are at least partially complementary to a polynucleotide that is antisense to the selected target polynucleotide;
• measuring the thermal melting point of a hybrid of an antisense oligonucleotide and the target polynucleotide or the polynucleotide that is antisense to the selected target polynucleotide under stringent hybridization conditions:
• and selecting at least one oligonucleotide for in vivo administration based on the information obtained.

A method of increasing expression of an IDUA polynucleotide or expression product thereof in a patient in need of treatment thereof comprising administration of an oligonucleotide that is at least 50% identical to a reverse complement of a natural antisense transcript to said IDUA polynucleotide to said patient and wherein the increase in expression of IDUA relative to a control is greater than about ten (10) percent.

A method of identifying and selecting an oligonucleotide to treat a patient in need of treatment thereof for an IDUA related disease or disorder comprising-identifying a patient having a deficiency in IDUA function;

• selecting cells or tissue from a patient having a deficiency in IDUA function;
• treating said cells or tissues with a plurality of oligonucleotides;
• determining the percentage increase of IDUA expression in the cells or tissues and selecting the oligonucleotide to administer to the patient.