Modulation of gene expression associated with inflammation proliferation and neurite outgrowth using nucleic acid based technologies

Abstract

The present invention relates to nucleic acid molecules, including antisense, enzymatic nucleic acid molecules, and RNA interference molecules, such as hammerhead ribozymes, DNAzymes, allozymes, siRNA, decoys and antisense, which modulate the expression of prostaglandin D2 (PTGDS), prostaglandin D2 receptor (PTGDR), adenosine receptor, NOGO and NOGO receptor, and IKK genes, such as IKK-gamma, IKK-alpha, or IKK-beta, and PKR genes.

1 . A nucleic acid molecule that down regulates expression or inhibits function of a receptor for a neurite growth inhibitor.  
     
     
         2 . A nucleic acid molecule of  claim 1 , wherein the receptor is a NOGO receptor.  
     
     
         3 . The nucleic acid of  claim 1 , wherein said nucleic acid molecule is adapted for use to treat conditions selected from the group consisting of CNS injury, spinal cord injury, and cerebrovascular accident.  
     
     
         4 . The nucleic acid molecule of  claim 1  or  claim 2 , wherein said nucleic acid molecule is an enzymatic nucleic acid molecule having at least one binding arm.  
     
     
         5 . The nucleic acid molecule of  claim 4 , wherein said enzymatic nucleic acid molecule has an endonuclease activity to cleave RNA encoded by a NOGO receptor gene.  
     
     
         6 . The nucleic acid of  claim 4 , wherein the at least one binding arm of the enzymatic nucleic acid molecule comprises a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1-1023.  
     
     
         7 . An enzymatic nucleic acid molecule comprising a sequence selected from the group consisting of SEQ ID NOs. 5484-7055.  
     
     
         8 . The nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule is an antisense nucleic acid molecule.  
     
     
         9 . An antisense nucleic acid molecule comprising a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1-1023.  
     
     
         10 . The enzymatic nucleic acid molecule of  claim 4 , wherein said enzymatic nucleic acid molecule is in a hammerhead (HH) motif.  
     
     
         11 . The enzymatic nucleic acid molecule of  claim 4 , wherein said enzymatic nucleic acid molecule is in a hairpin, hepatitis Delta virus, group I intron, VS nucleic acid, amberzyme, zinzyme or RNAse P nucleic acid motif.  
     
     
         12 . The enzymatic nucleic acid molecule of  claim 11 , wherein said zinzyme motif comprises a sequence selected from the group consisting of SEQ ID NOs. 6030-6272.  
     
     
         13 . The enzymatic nucleic acid molecule of  claim 11 , wherein said amberzyme motif comprises a sequence selected from the group consisting of SEQ ID NOs. 6630-7055.  
     
     
         14 . The enzymatic nucleic acid molecule of  claim 4 , wherein said enzymatic nucleic acid molecule is in a NCH motif.  
     
     
         15 . The enzymatic nucleic acid molecule of  claim 4 , wherein said enzymatic nucleic acid molecule is in a G-cleaver motif.  
     
     
         16 . The enzymatic nucleic acid molecule of  claim 4 , wherein said enzymatic nucleic acid molecule is a DNAzyme.  
     
     
         17 . The nucleic acid molecule of  claim 2 , wherein said nucleic acid molecule comprises between 12 and 100 bases complementary to RNA encoded by a NOGO receptor gene.  
     
     
         18 . The nucleic acid molecule of  claim 2 , wherein said nucleic acid molecule comprises between 14 and 24 bases complementary to the RNA encoded by a NOGO receptor gene.  
     
     
         19 . The nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule is chemically synthesized.  
     
     
         20 . The nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule comprises at least one 2′-sugar modification.  
     
     
         21 . The nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule comprises at least one nucleic acid base modification.  
     
     
         22 . The nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule comprises at least one phosphate backbone modification.  
     
     
         23 . A mammalian cell comprising the nucleic acid molecule of  claim 1 .  
     
     
         24 . The mammalian cell of  claim 23 , wherein said mammalian cell is a human cell.  
     
     
         25 . A method of reducing NOGO receptor activity in a cell, comprising the step of contacting said cell with the nucleic acid molecule of  claim 2 , under conditions suitable for said inhibition.  
     
     
         26 . A method of treatment of a patient having a condition associated with levels of a NOGO receptor, comprising contacting cells of said patient with the nucleic acid molecule of  claim 2 , under conditions suitable for said treatment.  
     
     
         27 . The method of  claim 26  further comprising the use of one or more drug therapies under conditions suitable for said treatment.  
     
     
         28 . A method of cleaving RNA encoded by a NOGO receptor gene comprising contacting the nucleic acid molecule of  claim 2  with said RNA under conditions suitable for the cleavage of said RNA.  
     
     
         29 . The method of  claim 28 , wherein said cleavage is carried out in the presence of a divalent cation.  
     
     
         30 . The method of  claim 29 , wherein said divalent cation is Mg 2+ .  
     
     
         31 . The nucleic acid molecule of  claim 1 , wherein said nucleic acid comprises a cap structure, wherein the cap structure is at the 5′-end, 3′-end, or both the 5′-end and the 3′-end.  
     
     
         32 . The enzymatic nucleic acid molecule of  claim 10 , wherein said hammerhead motif comprises a sequence selected from the group consisting of SEQ ID NOs. 5484-5583.  
     
     
         33 . The enzymatic nucleic acid molecule of  claim 14 , wherein said NCH motif comprises a sequence selected from the group consisting of SEQ ID NOs. 5584-6029.  
     
     
         34 . The enzymatic nucleic acid molecule of  claim 16 , wherein said DNAzyme comprises a sequence selected from the group consisting of SEQ ID NOs. 6273-6629.  
     
     
         35 . The method of  claim 25 , wherein said nucleic acid molecule is in a hammerhead motif.  
     
     
         36 . The method of  claim 25 , wherein said nucleic acid molecule is a DNAzyme.  
     
     
         37 . An expression vector comprising at least one nucleic acid molecule of  claim 1  in a manner that allows expression of the nucleic acid molecule.  
     
     
         38 . A mammalian cell comprising an expression vector of  claim 37 .  
     
     
         39 . The mammalian cell of  claim 38 , wherein said mammalian cell is a human cell.  
     
     
         40 . The expression vector of  claim 37 , wherein said expression vector encodes a nucleic acid molecule having a hammerhead motif.  
     
     
         41 . The expression vector of  claim 37 , wherein said expression vector further comprises a sequence for an antisense nucleic acid molecule complementary to RNA encoded by a NOGO receptor gene.  
     
     
         42 . The expression vector of  claim 37 , wherein said expression vector comprises a two or more of said nucleic acid molecules, which can be the same or different.  
     
     
         43 . The expression vector of  claim 42 , wherein said expression vector comprises a sequence encoding an antisense nucleic acid molecule complementary to RNA encoded by a NOGO receptor gene.  
     
     
         44 . A method for treatment of conditions selected from the group consisting of CNS injury and cerebrovascular accident comprising the step of administering to a patient the nucleic acid molecule of  claim 1  under conditions suitable for said treatment.  
     
     
         45 . The method of  claim 44 , wherein said treatment of CNS injury is treatment of spinal cord injury.  
     
     
         46 . A method for treatment of conditions selected from the group consisting of CNS injury and cerebrovascular accident comprising the step of administering to a patient the antisense nucleic acid molecule of  claim 9  under conditions suitable for said treatment.  
     
     
         47 . The method of  claim 44 , wherein said nucleic acid molecule is in a hammerhead motif.  
     
     
         48 . The method of  claim 44 , wherein said method further comprises administering to said patient one or more other therapies.  
     
     
         49 . The nucleic acid molecule of  claim 1 , wherein said nucleic acid molecule comprises at least five ribose residues, at least ten 2′-O-methyl modifications, and a 3′-end modification.  
     
     
         50 . The nucleic acid molecule of  claim 49 , wherein said nucleic acid molecule further comprises phosphorothioate linkages on at least three of the 5′ terminal nucleotides.  
     
     
         51 . The nucleic acid molecule of  claim 49 , wherein said 3′-end modification is 3′-3′ inverted abasic moiety.  
     
     
         52 . The enzymatic nucleic acid molecule of  claim 16 , wherein said DNAzyme comprises at least ten 2′-O-methyl modifications and a 3′-end modification.  
     
     
         53 . The enzymatic nucleic acid molecule of  claim 52 , wherein said DNAzyme further comprises phosphorothioate linkages on at least three of the 5′ terminal nucleotides.  
     
     
         54 . The enzymatic nucleic acid molecule of  claim 52 , wherein said 3′-end modification is 3′-3′ inverted abasic moiety.  
     
     
         55 . An enzymatic nucleic acid molecule that down regulates expression of a nucleic acid molecule encoding an IkappaB kinase (IKK) subunit.  
     
     
         56 . An enzymatic nucleic acid molecule that down regulates expression of a nucleic acid molecule encoding protein kinase PKR.  
     
     
         57 . An enzymatic nucleic acid molecule comprising a sequence selected from the group consisting of SEQ ID NOs. 7056-11665.  
     
     
         58 . An enzymatic nucleic acid molecule comprising at least one binding arm wherein one or more of said binding arms comprises a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1024-4414.  
     
     
         59 . An antisense nucleic acid molecule comprising a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1024-4414.  
     
     
         60 . The enzymatic nucleic acid molecule of any of claims  55 - 58 , wherein said enzymatic nucleic acid molecule is adapted to treat cancer.  
     
     
         61 . The antisense nucleic acid molecule of  claim 59 , wherein said antisense nucleic acid molecule is adapted to treat cancer.  
     
     
         62 . The enzymatic nucleic acid molecule of any of claims  55 - 58 , wherein said enzymatic nucleic acid molecule has an endonuclease activity to cleave RNA encoded by a IKK-gamma gene or PKR gene.  
     
     
         63 . The enzymatic nucleic acid molecule of  claim 55  or  claim 56 , wherein said enzymatic nucleic acid molecule is in an Inozyme configuration.  
     
     
         64 . The enzymatic nucleic acid molecule of  claim 55  or  claim 56 , wherein said enzymatic nucleic acid molecule is in a Zinzyme configuration.  
     
     
         65 . The enzymatic nucleic acid molecule of  claim 55  or  claim 56 , wherein said enzymatic nucleic acid molecule is in a G-cleaver configuration.  
     
     
         66 . The enzymatic nucleic acid molecule of  claim 55  or  claim 56 , wherein said enzymatic nucleic acid molecule is in an Amberzyme configuration.  
     
     
         67 . The enzymatic nucleic acid molecule of  claim 55  or  claim 56 , wherein said enzymatic nucleic acid molecule is in a DNAzyme configuration.  
     
     
         68 . The enzymatic nucleic acid molecule of  claim 55  or  claim 56 , wherein said enzymatic nucleic acid molecule is in a Hammerhead configuration.  
     
     
         69 . The enzymatic nucleic acid molecule of  claim 63 , wherein said Inozyme comprises a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1218-1721 and 3051-3549.  
     
     
         70 . The enzymatic nucleic acid molecule of  claim 63 , wherein said Inozyme comprises a sequence selected from the group consisting of SEQ ID NOs. 7250-7753 and 9701-10199.  
     
     
         71 . The enzymatic nucleic acid molecule of  claim 64 , wherein said Zinzyme comprises a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1722-1998 and 3550-3768.  
     
     
         72 . The enzymatic nucleic acid molecule of  claim 64 , wherein said Zinzyme comprises a sequence selected from the group consisting of SEQ ID NOs 7754-8030 and 10200-10418.  
     
     
         73 . The enzymatic nucleic acid molecule of  claim 66 , wherein said Amberzyme comprises a sequence selected from the group consisting of SEQ ID NOs 8441-9069 and 11001-11547.  
     
     
         74 . The enzymatic nucleic acid molecule of  claim 67 , wherein said DNAzyme comprises a sequence selected from the group consisting of SEQ ID NOs 8031-8440 and 10419-11000.  
     
     
         75 . The enzymatic nucleic acid molecule of  claim 68 , wherein said Hammerhead comprises a sequence complementary to a sequence selected from the group consisting of SEQ ID NOs. 1024-1217 and 2420-3050.  
     
     
         76 . The enzymatic nucleic acid molecule of  claim 68 , wherein said Hammerhead comprises a sequence selected from the group consisting of SEQ ID NOs 7056-7249 and 9070-9700.  
     
     
         77 . The enzymatic nucleic acid molecule of any of claims  55 - 58 , wherein said enzymatic nucleic acid molecule comprises between 12 and 100 bases complementary to RNA encoded by an IKK-gamma gene or PKR gene.  
     
     
         78 . The enzymatic nucleic acid molecule of any of claims  55 - 58 , wherein said enzymatic nucleic acid molecule comprises between 14 and 24 bases complementary to RNA encoded by an IKK-gamma gene or PKR gene.  
     
     
         79 . The enzymatic nucleic acid molecule of any of claims  55 - 58  wherein said enzymatic nucleic acid molecule is chemically synthesized.  
     
     
         80 . The antisense nucleic acid molecule of  claim 59 , wherein said antisense nucleic acid molecule is chemically synthesized.  
     
     
         81 . The enzymatic nucleic acid molecule of any of claims  55 - 58 , wherein said enzymatic nucleic acid molecule comprises at least one 2′-sugar modification.  
     
     
         82 . The antisense nucleic acid molecule of  claim 59 , wherein said antisense nucleic acid molecule comprises at least one 2′-sugar modification.  
     
     
         83 . The enzymatic nucleic acid molecule of any of claims  55 - 58 , wherein said enzymatic nucleic acid molecule comprises at least one nucleic acid base modification.  
     
     
         84 . The antisense nucleic acid molecule of  claim 59 , wherein said antisense nucleic acid molecule comprises at least one nucleic acid base modification.  
     
     
         85 . The enzymatic nucleic acid molecule of any of claims  55 - 58 , wherein said enzymatic nucleic acid molecule comprises at least one phosphate backbone modification.  
     
     
         86 . The antisense nucleic acid molecule of  claim 59 , wherein said antisense nucleic acid molecule comprises at least one phosphate backbone modification.  
     
     
         87 . A mammalian cell including the enzymatic nucleic acid molecule of any of claims  55 - 58 .  
     
     
         88 . The mammalian cell of  claim 87 , wherein said mammalian cell is a human cell.  
     
     
         89 . A method of down-regulating PKR activity in a cell, comprising contacting said cell with the enzymatic nucleic acid molecule of  claim 56 , under conditions suitable for down-regulating of PKR activity.  
     
     
         90 . A method of treatment of a patient having a condition associated with the level of PKR, comprising contacting cells of said patient with the enzymatic nucleic acid molecule of any of claims  55 - 59 , under conditions suitable for said treatment.  
     
     
         91 . A method of down-regulating IKK-gamma activity in a cell, comprising contacting said cell with the enzymatic nucleic acid molecule of any of claims  55 - 59 , under conditions suitable for down-regulating of IKK-gamma activity.  
     
     
         92 . A method of treatment of a patient having a condition associated with the level of IKK-gamma, comprising contacting cells of said patient with the enzymatic nucleic acid molecule of any of claims  55 - 59 , under conditions suitable for said treatment.  
     
     
         93 . The method of  claim 89  further comprising the use of one or more drug therapies under conditions suitable for said treatment.  
     
     
         94 . The method of  claim 90  further comprising the use of one or more drug therapies under conditions suitable for said treatment.  
     
     
         95 . The method of  claim 91  further comprising the use of one or more drug therapies under conditions suitable for said treatment.  
     
     
         96 . The method of  claim 92  further comprising the use of one or more drug therapies under conditions suitable for said treatment.  
     
     
         97 . A method of cleaving RNA encoded by a PKR gene comprising contacting an enzymatic nucleic acid molecule of  claim 56  with said RNA under conditions suitable for the cleavage.  
     
     
         98 . A method of cleaving RNA encoded by an IKK-gamma gene comprising contacting an enzymatic nucleic acid molecule of  claim 55  with said RNA under conditions suitable for the cleavage.  
     
     
         99 . The method of  claim 98 , wherein said cleavage is carried out in the presence of a divalent cation.  
     
     
         100 . The method of  claim 99 , wherein said cleavage is carried out in the presence of a divalent cation.  
     
     
         101 . The method of  claim 100 , wherein said divalent cation is Mg 2+ .  
     
     
         102 . The method of  claim 101 , wherein said divalent cation is Mg 2+ .  
     
     
         103 . The enzymatic nucleic acid molecule of any of claims  55 - 58 , wherein said enzymatic nucleic acid comprises a cap structure, wherein the cap structure is at the 5′-end, the 3′-end, or both the 5′-end and the 3′-end.  
     
     
         104 . The antisense nucleic acid molecule of  claim 59 , wherein said antisense nucleic acid comprises a cap structure, wherein the cap structure is at the 5′-end, the 3′-end, or both the 5′-end and the 3′-end.  
     
     
         105 . The enzymatic nucleic acid molecule of  claim 103 , wherein the cap structure at the 5′-end, 3′-end, or both the 5′-end and the 3′-end comprises a 3′,3′-linked or 5′,5′-linked deoxyabasic ribose derivative.  
     
     
         106 . The antisense nucleic acid molecule of  claim 104 , wherein the cap structure at the 5′-end, 3′-end, or both the 5′-end and the 3′-end comprises a 3′,3′-linked or 5′,5′-linked deoxyabasic ribose derivative.  
     
     
         107 . The method of  claim 89 , wherein said enzymatic nucleic acid molecule is in a Zinzyme configuration.  
     
     
         108 . An expression vector comprising at least one enzymatic nucleic acid molecule of  claim 55  or  claim 56  in a manner that allows expression of the nucleic acid molecule.  
     
     
         109 . A mammalian cell comprising the expression vector of  claim 108 .  
     
     
         110 . The mammalian cell of  claim 109 , wherein said mammalian cell is a human cell.  
     
     
         111 . The expression vector of  claim 108 , wherein said enzymatic nucleic acid molecule is in a hammerhead configuration. (DOES THIS MAKE SENSE?)  
     
     
         112 . The expression vector of  claim 108 , wherein said expression vector further comprises a sequence for an antisense nucleic acid molecule complementary to RNA encoded by an IKK-gamma subunit gene or PKR gene.  
     
     
         113 . The expression vector of  claim 108 , wherein said expression vector comprises a nucleic acid sequence encoding two or more of said enzymatic nucleic acid molecules, which can be the same or different.  
     
     
         114 . The expression vector of  claim 108 , wherein said expression vector further comprises a sequence encoding an antisense nucleic acid molecule complementary to RNA encoded by an IKK-gamma gene or PKR gene.  
     
     
         115 . A method for treatment of cancer comprising administering to a patient the enzymatic nucleic acid molecule of any of claims  55 - 58  under conditions suitable for said treatment.  
     
     
         116 . The method of  claim 115 , wherein said cancer is breast cancer, lung cancer, prostate cancer, colorectal cancer, brain cancer, esophageal cancer, stomach cancer, bladder cancer, pancreatic cancer, cervical cancer, head and neck cancer, ovarian cancer, melanoma, lymphoma, glioma, or multidrug resistant cancer.  
     
     
         117 . A method for treatment of cancer comprising administering to a patient the antisense nucleic acid molecule of  claim 59  under conditions suitable for said treatment.  
     
     
         118 . The method of  claim 117 , wherein said cancer is breast cancer, lung cancer, prostate cancer, colorectal cancer, brain cancer, esophageal cancer, stomach cancer, bladder cancer, pancreatic cancer, cervical cancer, head and neck cancer, ovarian cancer, melanoma, lymphoma, glioma, or multidrug resistant cancer.  
     
     
         119 . The method of  claim 115 , wherein said enzymatic nucleic acid molecule is in a Zinzyme configuration.  
     
     
         120 . The method of  claim 115 , wherein said method further comprises administering to said patient one or more other therapies.  
     
     
         121 . The method of  claim 117 , wherein said method further comprises administering to said patient one or more other therapies.  
     
     
         122 . The nucleic acid molecule of any of claims  55 ,  56 , or  58 , wherein said nucleic acid molecule comprises at least five ribose residues, at least ten 2′-O-methyl modifications, and a 3′-end modification.  
     
     
         123 . The nucleic acid molecule of  claim 122 , wherein said nucleic acid molecule further comprises phosphorothioate linkages on at least three of the 5′ terminal nucleotides.  
     
     
         124 . The nucleic acid molecule of  claim 122 , wherein said 3′-end modification is a 3′-3′ inverted abasic moiety.  
     
     
         125 . The method of  claim 93  wherein said other drug therapies are monoclonal antibodies, IKK-gamma or PKR-specific inhibitors, chemotherapy, or radiation therapy.  
     
     
         126 . The method of  claim 125 , wherein said chemotherapy is paclitaxel, docetaxel, cisplatin, methotrexate, cyclophosphamide, doxorubin, fluorouracil carboplatin, edatrexate, gemcitabine, or vinorelbine.  
     
     
         127 . The method of  claim 94  wherein said other drug therapies are monoclonal antibodies, IKK-gamma or PKR-specific inhibitors, chemotherapy, or radiation therapy.  
     
     
         128 . The method of  claim 127 , wherein said chemotherapy is paclitaxel, docetaxel, cisplatin, methotrexate, cyclophosphamide, doxorubin, fluorouracil carboplatin, edatrexate, gemcitabine, or vinorelbine.  
     
     
         129 . The method of  claim 95  wherein said other drug therapies are monoclonal antibodies, IKK-gamma or PKR-specific inhibitors, chemotherapy, or radiation therapy.  
     
     
         130 . The method of  claim 129 , wherein said chemotherapy is paclitaxel, docetaxel, cisplatin, methotrexate, cyclophosphamide, doxorubin, fluorouracil carboplatin, edatrexate, gemcitabine, or vinorelbine.  
     
     
         131 . The method of  claim 96  wherein said other drug therapies are monoclonal antibodies, IKK-gamma or PKR-specific inhibitors, chemotherapy, or radiation therapy.  
     
     
         132 . The method of  claim 131 , wherein said chemotherapy is paclitaxel, docetaxel, cisplatin, methotrexate, cyclophosphamide, doxorubin, fluorouracil carboplatin, edatrexate, gemcitabine, or vinorelbine.  
     
     
         133 . The method of  claim 120 , wherein said other therapies are monoclonal antibodies, IKK-gamma or PKR-specific inhibitors, chemotherapy, or radiation therapy.  
     
     
         134 . The method of  claim 133 , wherein said chemotherapy is paclitaxel, docetaxel, cisplatin, methotrexate, cyclophosphamide, doxorubin, fluorouracil carboplatin, edatrexate, gemcitabine, or vinorelbine.  
     
     
         135 . The method of  claim 121 , wherein said other therapies are monoclonal antibodies, IKK-gamma or PKR-specific inhibitors, chemotherapy, or radiation therapy.  
     
     
         136 . The method of  claim 135 , wherein said chemotherapy is paclitaxel, docetaxel, cisplatin, methotrexate, cyclophosphamide, doxorubin, fluorouracil carboplatin, edatrexate, gemcitabine, or vinorelbine.  
     
     
         137 . A method for treatment of an inflammatory disease comprising the step of administering to a patient the enzymatic nucleic acid molecule of any of claims  55 - 58  under conditions suitable for said treatment.  
     
     
         138 . The method of  claim 137 , wherein said inflammatory disease is rheumatoid arthritis, restenosis, asthma, Crohn's disease, diabetes, obesity, autoimmune disease, lupus, multiple sclerosis, transplant/graft rejection, gene therapy applications, ischemia/reperfusion injury, glomerulonephritis, sepsis, allergic airway inflammation, inflammatory bowel disease, or infection.  
     
     
         139 . A method for treatment of an inflammatory disease comprising the step of administering to a patient the antisense nucleic acid molecule of  claim 59  under conditions suitable for said treatment.  
     
     
         140 . The method of  claim 139 , wherein said inflammatory disease is rheumatoid arthritis, restenosis, asthma, Crohn's disease, diabetes, obesity, autoimmune disease, lupus, multiple sclerosis, transplant/graft rejection, gene therapy applications, ischemia/reperfusion injury (CNS and myocardial), glomerulonephritis, sepsis, allergic airway inflammation, inflammatory bowel disease, or infection.  
     
     
         141 . The method of  claim 137 , wherein said enzymatic nucleic acid molecule is in a Zinzyme configuration.  
     
     
         142 . The method of  claim 137 , wherein said method further comprises administering to said patient one or more other therapies.  
     
     
         143 . The method of  claim 139 , wherein said method further comprises administering to said patient one or more other therapies.  
     
     
         144 . A pharmaceutical composition comprising an enzymatic nucleic acid molecule of any of claims  55 - 58  in a pharmaceutically acceptable carrier.  
     
     
         145 . A pharmaceutical composition comprising an antisense nucleic acid molecule of  claim 59  in a pharmaceutically acceptable carrier.  
     
     
         146 . The enzymatic nucleic acid molecule of  claim 55 , wherein said subunit of IKK-is IKK-gamma.  
     
     
         147 . The enzymatic nucleic acid molecule of  claim 55 , wherein said subunit of IKK-is IKK-alpha.  
     
     
         148 . The enzymatic nucleic acid molecule of  claim 55 , wherein said subunit of IKK-is IKK-beta.  
     
     
         149 . A method of administering to a cell an enzymatic nucleic acid molecule of any of claims  55 - 57  comprising contacting said cell with the enzymatic nucleic acid molecule under conditions suitable for said administration.  
     
     
         150 . The method of  claim 149 , wherein said cell is a mammalian cell.  
     
     
         151 . The method of  claim 149 , wherein said cell is a human cell.  
     
     
         152 . The method of  claim 149 , wherein said administration is in the presence of a delivery reagent.  
     
     
         153 . The method of  claim 152 , wherein said delivery reagent is a lipid.  
     
     
         154 . The method of  claim 153 , wherein said lipid is a cationic lipid.  
     
     
         155 . The method of  claim 153 , wherein said lipid is a phospholipid.  
     
     
         156 . The method of  claim 152 , wherein said delivery reagent is a liposome.  
     
     
         157 . A nucleic acid molecule that down regulates expression of a prostaglandin D2 receptor (PTGDR) gene.  
     
     
         158 . The nucleic acid molecule of  claim 157 , wherein said nucleic acid molecule is an enzymatic nucleic acid molecule.  
     
     
         159 . The nucleic acid molecule of  claim 157 , wherein said nucleic acid molecule is an antisense nucleic acid molecule.  
     
     
         160 . The enzymatic nucleic acid molecule of  claim 158 , wherein said enzymatic nucleic acid molecule comprises a sequence selected from the group of sequences consisting of SEQ ID NOs: 11666-13262.  
     
     
         161 . The enzymatic nucleic acid molecule of  claim 158 , wherein said enzymatic nucleic acid molecule comprises at least one binding arm wherein the at least one binding arm comprises a sequence complementary to a sequence selected from the group of sequences consisting of SEQ ID NOs: 4415-5483.  
     
     
         162 . The antisense nucleic acid molecule of  claim 159 , wherein said antisense nucleic acid molecule comprises a sequence complementary to a sequence selected from the group of sequences consisting of SEQ ID NOs: 4415-5483.  
     
     
         163 . The nucleic acid molecule of  claim 157 , wherein said nucleic acid molecule is adapted to treat asthma.  
     
     
         164 . The enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , wherein said enzymatic nucleic acid molecule has an endonuclease activity to cleave RNA encoded by a PTGDR gene.  
     
     
         165 . The enzymatic nucleic acid molecule of  claim 157 , wherein said enzymatic nucleic acid molecule is in a hammerhead configuration.  
     
     
         166 . The enzymatic nucleic acid molecule of  claim 157 , wherein said enzymatic nucleic acid molecule is in an Inozyme configuration.  
     
     
         167 . The enzymatic nucleic acid molecule of  claim 157 , wherein said enzymatic nucleic acid molecule is in a Zinzyme configuration.  
     
     
         168 . The enzymatic nucleic acid molecule of  claim 157 , wherein said enzymatic nucleic acid molecule is in a DNAzyme configuration.  
     
     
         169 . The enzymatic nucleic acid molecule of  claim 157 , wherein said enzymatic nucleic acid molecule is in a G-cleaver configuration.  
     
     
         170 . The enzymatic nucleic acid molecule of  claim 157 , wherein said enzymatic nucleic acid molecule is in an Amberzyme configuration.  
     
     
         171 . The enzymatic nucleic acid molecule of  claim 165 , wherein said hammerhead configuration comprises a sequence complementary to a sequence selected from the group of sequences consisting of SEQ ID NOs: 4415-4641.  
     
     
         172 . The enzymatic nucleic acid molecule of  claim 165 , wherein said hammerhead configuration comprises a sequence selected from the group of sequences consisting of SEQ ID NOs: 11666-11892.  
     
     
         173 . The enzymatic nucleic acid molecule of  claim 166 , wherein said Inozyme configuration comprises a sequence complementary to a sequence selected from the group of sequences consisting of SEQ ID NOs: 4642-5017.  
     
     
         174 . The enzymatic nucleic acid molecule of  claim 166 , wherein said Inozyme configuration comprises a sequence selected from the group of sequences consisting of SEQ ID NOs: 11893-12268.  
     
     
         175 . The enzymatic nucleic acid molecule of  claim 167 , wherein said Zinzyme configuration comprises a sequence complementary to a sequence selected from the group of sequences consisting of SEQ ID NOs: 5018-5248.  
     
     
         176 . The enzymatic nucleic acid molecule of  claim 167 , wherein said Zinzyme configuration comprises a sequence selected from the group of sequences consisting of SEQ ID NOs: 12269-12499.  
     
     
         177 . The enzymatic nucleic acid molecule of  claim 168 , wherein said DNAzyme configuration comprises a sequence complementary to a sequence selected from the group of sequences consisting of SEQ ID NOs: 4415-5294.  
     
     
         178 . The enzymatic nucleic acid molecule of  claim 168 , wherein said DNAzyme configuration comprises a sequence selected from the group of sequences consisting of SEQ ID NOs: 12500-12842.  
     
     
         179 . The enzymatic nucleic acid molecule of  claim 170 , wherein said Amberzyme configuration comprises a sequence complementary to a sequence selected from the group of sequences consisting of SEQ ID NOs: 5018-5248, and 5295-5483.  
     
     
         180 . The enzymatic nucleic acid molecule of  claim 170 , wherein said Amberzyme configuration comprises a sequence selected from the group of sequences consisting of SEQ ID NOs: 12843-13262.  
     
     
         181 . The enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , wherein said enzymatic nucleic acid molecule comprises between 8 and 100 bases complementary to a RNA molecule encoded by a PTGDR gene.  
     
     
         182 . The enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , wherein said enzymatic nucleic acid molecule comprises between 14 and 24 bases complementary to a RNA molecule encoded by a PTGDR gene.  
     
     
         183 . The enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , wherein said enzymatic nucleic acid molecule is chemically synthesized.  
     
     
         184 . The antisense nucleic acid molecule of  claim 159 , wherein said antisense nucleic acid molecule is chemically synthesized.  
     
     
         185 . The enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , wherein said enzymatic nucleic acid molecule comprises at least one 2′-sugar modification.  
     
     
         186 . The antisense nucleic acid molecule of  claim 159 , wherein said antisense nucleic acid molecule comprises at least one 2′-sugar modification.  
     
     
         187 . The enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , wherein said enzymatic nucleic acid molecule comprises at least one nucleic acid base modification.  
     
     
         188 . The antisense nucleic acid molecule of  claim 159 , wherein said antisense nucleic acid molecule comprises at least one nucleic acid base modification.  
     
     
         189 . The enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , wherein said enzymatic nucleic acid molecule comprises at least one phosphate backbone modification.  
     
     
         190 . The antisense nucleic acid molecule of  claim 159 , wherein said antisense nucleic acid molecule comprises at least one phosphate backbone modification.  
     
     
         191 . A mammalian cell comprising the enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 .  
     
     
         192 . The mammalian cell of  claim 191 , wherein said mammalian cell is a human cell.  
     
     
         193 . A method of reducing PTGDR activity in a cell, comprising contacting said cell with the enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , under conditions suitable for said reduction.  
     
     
         194 . A method of reducing PTGDR activity in a cell, comprising contacting said cell with the antisense nucleic acid molecule of  claim 159  under conditions suitable for said reduction.  
     
     
         195 . A method of treatment of a patient having a condition associated with the level of PTGDR, comprising contacting cells of said patient with the enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , under conditions suitable for said treatment.  
     
     
         196 . A method of treatment of a patient having a condition associated with the level of PTGDR, comprising contacting cells of said patient with the antisense nucleic acid molecule of  claim 159 , under conditions suitable for said treatment.  
     
     
         197 . The method of  claim 193  further comprising the use of one or more drug therapies under conditions suitable for said treatment.  
     
     
         198 . The method of  claim 194  further comprising the use of one or more drug therapies under conditions suitable for said treatment.  
     
     
         199 . The method of  claim 195  further comprising the use of one or more drug therapies under conditions suitable for said treatment.  
     
     
         200 . The method of  claim 196  further comprising the use of one or more drug therapies under conditions suitable for said treatment.  
     
     
         201 . A method of cleaving a RNA molecule encoded by a PTGDR gene comprising contacting the enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161  with said RNA molecule encoded by a PTGDR gene under conditions suitable for the cleavage.  
     
     
         202 . The method of  claim 201 , wherein said cleavage is carried out in the presence of a divalent cation.  
     
     
         203 . The method of  claim 202 , wherein said divalent cation is Mg 2+ .  
     
     
         204 . The enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , wherein said enzymatic nucleic acid comprises a cap structure, wherein the cap structure is at the 5′-end, 3′-end, or both the 5′-end and the 3′-end.  
     
     
         205 . The antisense nucleic acid molecule of  claim 159 , wherein said antisense nucleic acid comprises a cap structure, wherein the cap structure is at the 5′-end, 3′-end, or both the 5′-end and the 3′-end.  
     
     
         206 . The enzymatic nucleic acid molecule of  claim 204 , wherein the cap structure at the 5′-end, 3′-end, or both the 5′-end and the 3′-end comprises a 3′,3′-linked or 5′,5′-linked deoxyabasic ribose derivative.  
     
     
         207 . The antisense nucleic acid molecule of  claim 205 , wherein the cap structure at the 5′-end, 3′-end, or both the 5′-end and the 3′-end comprises a 3′,3′-linked or 5′,5′-linked deoxyabasic ribose derivative.  
     
     
         208 . The method of  claim 193 , wherein said enzymatic nucleic acid molecule is in a Zinzyme configuration.  
     
     
         209 . An expression vector comprising a nucleic acid molecule encoding at least one enzymatic nucleic acid molecule of  claim 158  or  claim 160  in a manner that allows expression of the nucleic acid molecule.  
     
     
         210 . A mammalian cell comprising the expression vector of  claim 209 .  
     
     
         211 . The mammalian cell of  claim 210 , wherein said mammalian cell is a human cell.  
     
     
         212 . The expression vector of  claim 209 , wherein said enzymatic nucleic acid molecule is in a hammerhead configuration.  
     
     
         213 . The expression vector of  claim 209 , wherein said expression vector further comprises a sequence for an antisense nucleic acid molecule complementary to a RNA molecule encoded by a PTGDR gene.  
     
     
         214 . The expression vector of  claim 209 , wherein said expression vector comprises a nucleic acid sequence encoding two or more of said enzymatic nucleic acid molecules, which can be the same or different.  
     
     
         215 . The expression vector of  claim 214 , wherein said expression vector further comprises a sequence encoding an antisense nucleic acid molecule complementary to a RNA molecule encoded by a PTGDR gene.  
     
     
         216 . A method for treatment of an allergic condition comprising the step of administering to a patient the enzymatic nucleic acid molecule of any of claims  156 - 159  under conditions suitable for said treatment.  
     
     
         217 . The method of  claim 216 , wherein said allergic condition is asthma, allergic rhinitis, or atopic dermatitis.  
     
     
         218 . A method for treatment of an allergic condition comprising administering to a patient the antisense nucleic acid molecule of  claim 159  under conditions suitable for said treatment.  
     
     
         219 . The method of  claim 218 , wherein said allergic condition is asthma, allergic rhinitis, or atopic dermatitis.  
     
     
         220 . The method of  claim 216 , wherein said enzymatic nucleic acid molecule is in a Zinzyme configuration.  
     
     
         221 . The method of  claim 216 , wherein said method further comprises administering to said patient one or more other treatment therapies.  
     
     
         222 . The method of  claim 218 , wherein said method further comprises administering to said patient one or more other treatment therapies.  
     
     
         223 . The enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 , wherein said enzymatic nucleic acid molecule comprises at least five ribose residues, at least ten 2′-O-methyl modifications, and a 3′-end modification.  
     
     
         224 . The enzymatic nucleic acid molecule of  claim 223 , wherein said enzymatic nucleic acid molecule further comprises phosphorothioate linkages on at least three of the 5′ terminal nucleotides.  
     
     
         225 . The nucleic acid molecule of  claim 223 , wherein said 3′-end modification is a 3′-3′ inverted abasic moiety.  
     
     
         226 . The method of  claim 197  wherein said other drug therapies are bronchodilators, anti-inflammatories, adenosine inhibitors, or adenosine A1 receptor inhibitors.  
     
     
         227 . A pharmaceutical composition comprising an enzymatic nucleic acid molecule of any of claims  158 ,  160  or  161 .  
     
     
         228 . A pharmaceutical composition comprising an antisense nucleic acid molecule of  claim 159 .  
     
     
         229 . A method of administering to a mammal the nucleic acid molecule of  claim 157 , comprising contacting said mammal with the nucleic acid molecule under conditions suitable for said administration.  
     
     
         230 . The method of  claim 229 , wherein said mammal is a human.  
     
     
         231 . The method of  claim 229  wherein said administration is in the presence of a delivery reagent.  
     
     
         232 . The method of  claim 231 , wherein said delivery reagent is a lipid.  
     
     
         233 . The method of  claim 232 , wherein said lipid is a cationic lipid.  
     
     
         234 . The method of  claim 232 , wherein said lipid is a phospholipid.  
     
     
         235 . The method of  claim 231 , wherein said delivery reagent is a liposome.