Methods and compositions for reducing activity of the atrial natriuretic peptide receptor and for treatment of diseases
First Claim
1. A method for reducing activity of a natriuretic peptide receptor comprising:
- selecting a polynucleotide whereinthe polynucleotide is a polynucleotide complementary with a portion of a natriuretic peptide receptor gene;
orthe polynucleotide is a polynucleotide complementary with a portion of a natriuretic peptide receptor messenger RNA;
orthe polynucleotide is a polynucleotide encoding the polynucleotide complementary with a portion of the natriuretic peptide receptor messenger RNA;
and administering the selected polynucleotide or a combination such that the selected polynucleotide or the combination reduces or inhibits expression of a natriuretic peptide receptor gene.
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Abstract
Methods, compositions and devices are provided by the present invention for reducing activity of a natriuretic peptide receptor and other signals. Therapeutic treatments are provided by use of polynucleotides encoding a natriuretic peptide or by regulating the expression of natriuretic peptide receptor, such as NPRA and NPRC, or combinations of these therapies. Routes used for delivering polynucleotides encoding a natriuretic peptide, or, for example, siRNA that down regulates natriuretic peptide receptor include subcutaneous injection, oral gavage, transdermal and intranasal delivery routes. Compositions can include chitosan, chitosan derivatives, and chitosan derivative and a lipid. Transdermal delivery can use a transdermal cream. Intranasal delivery can use a dropper or an aspirator for delivery of a mist. Oral gavage delivers equivalent to oral delivery. Delivery permits cell and tissue specific targeting of gene therapies resulting in expression of a natriuretic peptide or down regulation of natriuretic peptide receptor. A variety of cancers, asthma and viral diseases can be treated therapeutically using the methods and compositions of the present invention.
124 Citations
68 Claims
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1. A method for reducing activity of a natriuretic peptide receptor comprising:
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selecting a polynucleotide wherein the polynucleotide is a polynucleotide complementary with a portion of a natriuretic peptide receptor gene;
orthe polynucleotide is a polynucleotide complementary with a portion of a natriuretic peptide receptor messenger RNA;
orthe polynucleotide is a polynucleotide encoding the polynucleotide complementary with a portion of the natriuretic peptide receptor messenger RNA; and administering the selected polynucleotide or a combination such that the selected polynucleotide or the combination reduces or inhibits expression of a natriuretic peptide receptor gene. - View Dependent Claims (2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 60, 63, 64)
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17. A method for treating an inflammatory disorder, a viral infection or a cell proliferation disorder treatable by inducing apoptosis, comprising:
- selecting a polynucleotide, wherein the polynucleotide is a polynucleotide encoding a natriuretic hormone peptide operably linked to a tissue specific promoter, or the polynucleotide is a polynucleotide complementary with a portion of a natriuretic peptide receptor gene or the polynucleotide is complementary with a portion of a natriuretic peptide receptor messenger RNA or a polynucleotide encoding a natriuretic peptide receptor, or the polynucleotide includes a plurality of polynucleotides including a combination of any of the following polynucleotides where the combination includes a polynucleotide encoding a natriuretic hormone peptide and an operably linked promoter and a polynucleotide complementary with a portion of a natriuretic peptide receptor gene or a polynucleotide complementary with a portion of a natriuretic peptide receptor messenger RNA or a polynucleotide encoding a natriuretic peptide receptor; and
administering or delivering an effective amount of the selected polynucleotide to a person or animal in need of treatment. - View Dependent Claims (18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 65, 66, 67, 68)
- selecting a polynucleotide, wherein the polynucleotide is a polynucleotide encoding a natriuretic hormone peptide operably linked to a tissue specific promoter, or the polynucleotide is a polynucleotide complementary with a portion of a natriuretic peptide receptor gene or the polynucleotide is complementary with a portion of a natriuretic peptide receptor messenger RNA or a polynucleotide encoding a natriuretic peptide receptor, or the polynucleotide includes a plurality of polynucleotides including a combination of any of the following polynucleotides where the combination includes a polynucleotide encoding a natriuretic hormone peptide and an operably linked promoter and a polynucleotide complementary with a portion of a natriuretic peptide receptor gene or a polynucleotide complementary with a portion of a natriuretic peptide receptor messenger RNA or a polynucleotide encoding a natriuretic peptide receptor; and
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38. A polynucleotide comprising:
- a polynucleotide encoding a polynucleotide complementary with a portion of a natriuretic peptide receptor A messenger RNA, such that the polynucleotide complementary with a portion of a natriuretic peptide receptor A messenger RNA reduces or inhibits expression of a natriuretic peptide receptor A gene.
- View Dependent Claims (39)
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40. A method for reducing activity of a natriuretic peptide receptor comprising:
- selecting a polynucleotide means for reducing or inhibiting expression of a natriuretic peptide receptor;
providing a means for delivering the polynucleotide means to cells in vivo; and
administering the polynucleotide means using the means for delivering. - View Dependent Claims (41, 42, 43)
- selecting a polynucleotide means for reducing or inhibiting expression of a natriuretic peptide receptor;
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44. A pharmaceutical composition comprising:
- a polynucleotide encoding a polynucleotide complementary with a portion of a natriuretic peptide receptor messenger RNA such that activity of a natriuretic peptide receptor gene is regulated when the polynucleotide is administered in vivo.
- View Dependent Claims (45, 46, 47, 48, 49, 50, 51, 52)
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53. A therapeutic device, comprising:
- a polynucleotide encoding a peptide that comprises the amino acid sequence of SEQ ID No. 5;
a chitosan or chitosan derivative complexed with the polynucleotide to form a complex; and
a means for delivering the complex in vivo therapeutically. - View Dependent Claims (54, 55, 56, 57)
- a polynucleotide encoding a peptide that comprises the amino acid sequence of SEQ ID No. 5;
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58. A method of therapeutically treating a disorder, comprising:
- deactivating NFκ
B, or reducing or inhibiting expression or activity of NFκ
B, by administering an effective amount of a polynucleotide or polypeptide or agent that reduces or inhibits expression or activity of NFκ
B to a person or animal in need of treatment. - View Dependent Claims (59)
- deactivating NFκ
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61. A method for reducing activity or expression of a natriuretic peptide receptor in a cell, the method comprising contacting or delivering to the cell an effective amount of a polynucleotide encoding a natriuretic peptide, or an effective amount of a polynucleotide having a nucleotide sequence that is complementary with a portion of a natriuretic peptide receptor gene, or an effective amount of a polynucleotide encoding a siRNA complementary with a portion of a natriuretic peptide receptor messenger RNA or complementary with a nucleic acid sequence encoding a natriuretic peptide receptor.
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62. A method for reducing activity or expression of a natriuretic peptide receptor in a cell of a person or animal, said the method comprising administering to the person or animal an effective amount of a polynucleotide encoding a natriuretic peptide, or an effective amount of a polynucleotide having a nucleotide sequence that is complementary with a portion of a natriuretic peptide receptor gene or an effective amount of a polynucleotide encoding a polynucleotide complementary with a portion of a natriuretic peptide receptor messenger RNA or complementary with a nucleic acid sequence encoding a natriuretic peptide receptor.
Specification