US2003166281A1PendingUtilityA1
Methods of discovering chemicals capable of functioning as gene expression modulators
Est. expiryJul 18, 2009(expired)· nominal 20-yr term from priority
A61K 48/00A61K 31/7068C07K 14/775Y02A50/30C12Q 1/6886C12Q 2600/136C12N 15/67C12Q 1/6897
60
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Claims
Abstract
The present invention provides a method of transcriptionally modulating the expression of a gene-of-interest. The method comprises contacting a cell which is capable of expressing the gene with an amount of a molecule effective to transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene which is expressed by the cell. Molecules useful in the practice of the invention are characterized as follows (a) do not naturally occur in the cell, (b) bind to DNA or RNA or bind to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell. Additionally, this invention provides a method for determining whether a molecule known to be a modulator of protein biosynthesis is capable of transcriptionally modulating expression of a gene-of-interest.
Claims
exact text as granted — not AI-modifiedWhat is claimed is:
1 . A method of transcriptionally modulating the expression of a homologous gene-of-interest, the expression of which is associated with a defined physiological or pathological effect within a multicellular organism, which comprises contacting a cell, which is capable of expressing the gene, with an amount of a molecule effective to transcriptionally modulate expression of the gene and thereby affect the level of the protein encoded by the gene which is expressed by the cell, which molecule (a) does not naturally occur in the cell, (b) specifically transcriptionally modulates expression of the gene-of-interest, and (c) binds to DNA or RNA, or binds to a protein through a domain of such protein which is not a ligand-binding domain of a receptor which naturally occurs in the cell, the binding of a ligand to which ligand-binding domain is normally associated with the defined physiological or pathological effect.
2 . A method of claim 1 , wherein the molecule does not naturally occur in any cell of a higher eucaryotic organism.
3 . A method of claim 1 , wherein the molecule does not naturally occur in any cell.
4 . A method of claim 1 , wherein the molecule is not a naturally occurring molecule.
5 . A method of claim 1 , wherein the cell is a cell of the multicellular organism.
6 . A method of claim 1 , wherein the cell is an animal cell.
7 . A method of claim 6 , wherein the animal cell is a human cell.
8 . A method of claim 1 , wherein the cell is a plant cell.
9 . A method of claim 1 , wherein the cell is a fungal cell.
10 . A method of claim 1 , wherein the cell is a protozoan cell.
11 . A method of claim 1 , wherein the cell is a bacterial cell.
12 . A method of claim 1 , wherein the gene-of-interest is a human gene.
13 . A method of claim 1 , wherein the gene-of-interest encodes a hematopoietic protein.
14 . A method of claim 13 , wherein the hematopoietic protein is a colony stimulating factor.
15 . A method of claim 14 , wherein the colony stimulating factor is granulocyte-macrophage colony stimulating factor (GM-CSF).
16 . A method of claim 14 , wherein the colony stimulating factor is granulocyte colony stimulating factor (G-CSF).
17 . A method of claim 14 , wherein the colony stimulating factor is macrophage colony stimulating factor (M-CSF).
18 . A method of claim 13 , wherein the hematopoietic protein is erythropoietin (EPO).
19 . A method of claim 1 , wherein the gene-of-interest encodes an interleukin (IL).
20 . A method of claim 1 , wherein the gene-of-interest encodes a growth hormone selected from the group consisting of human, bovine, porcine, avian, ovine, piscine, and equine growth hormone, and polypeptide analogs thereof having the biological activity of the corresponding naturally occurring growth hormone.
21 . A method of claim 1 , wherein the gene-of-interest encodes a growth hormone releasing factor.
22 . A method of claim 1 , wherein the gene-of-interest is a viral gene.
23 . A method of claim 22 , wherein the viral gene is a retroviral gene.
24 . A method of claim 23 , wherein the retroviral gene is a gene from the HIV, HTLV-1, or HTLV-2 virus.
25 . A method of claim 22 , wherein the viral gene is a gene from a hepatitis virus.
26 . A method of claim 22 , wherein the viral gene is a gene from a herpes virus.
27 . A method of claim 22 , wherein the viral gene is a gene from an animal virus.
28 . A method of claim 22 , wherein the viral gene is a gene from a papilloma virus.
29 . A method of claim 22 , wherein the viral gene is a gene from a cytomegalovirus.
30 . A method of claim 27 , wherein the animal virus is a pseudorabies, Marek's, Newcastle's Disease, or IBR virus.
31 . A method of claim 1 , wherein the gene-of-interest is a plant gene.
32 . A method of claim 31 , wherein the plant gene encodes an agronomically important trait.
33 . A method of claim 32 , wherein the agronomically important trait is selected from the group consisting of germination, sprouting, flowering, fruit ripening, salt tolerance, herbicide resistance, pesticide resistance, fungicide resistance, temperature resistance, and growth.
34 . A method of claim 1 , wherein the gene-of-interest is a protozoan gene.
35 . A method of claim 34 , wherein the protozoan is selected from the group consisting of Trypanosoma, Plasmodium, Leishmania, Giardia, Entamoeba, Toxoplasma, Babesia, and Cryptosporidiosis.
36 . A method of claim 1 , wherein the gene-of-interest is a helminth gene.
37 . A method of claim 1 , wherein the gene-of-interest is an oncogene.
38 . A method of claim 37 , wherein the oncogene is the phl-abl oncogene.
39 . A method of claim 37 , wherein the oncogene is selected from the group consisting of H-, N-, and K-ras oncogenes.
40 . A method of claim 37 , wherein the oncogene is the neu oncogene.
41 . A method of claim 37 , wherein the oncogene is the src oncogene.
42 . A method of claim 1 , wherein the gene-of-interest encodes TGF-β1.
43 . A method of claim 1 , wherein the gene-of-interest encodes TGF-β2.
44 . A method of claim 1 , wherein the gene-of-interest encodes TGF-β3.
45 . A method of claim 1 , wherein the gene-of-interest encodes a naturally occurring receptor.
46 . A method of claim 45 , wherein the receptor is a TGF-β receptor.
47 . A method of claim 45 , wherein the receptor is a testosterone receptor.
48 . A method of claim 45 , wherein the receptor is an estrogen receptor.
49 . A method of claim 45 , wherein the receptor is the human low density lipoprotein (LDL) receptor.
50 . A method of claim 45 , wherein the receptor is the receptor for a hematopoietic protein selected from the group consisting of M-CSF, G-CSF, GM-CSF, and EPO.
51 . A method of claim 45 , wherein the receptor is the receptor for an interleukin (IL) selected from the group consisting of IL-1, IL-2, IL-3, IL-4, IL-5, IL-6, IL-7and IL-8.
52 . A method of claim 45 , wherein the receptor is a cell surface protein which mediates infection of the cell by a virus.
53 . A method of claim 52 , wherein the virus is selected from the group consisting of HIV, HTLV-1, HTLV-2, a hepatitis virus, a herpes virus, an animal virus, a papilloma virus, a cytomegalovirus, and a rhinovirus.
54 . A method of claim 1 , wherein the receptor which naturally occurs in the cell is a testosterone receptor.
55 . A method of claim 1 , wherein the receptor which naturally occurs in the cell is an estrogen receptor.
56 . A method of claim 1 , wherein in (c) the protein is not the protein encoded by the gene-of-interest.
57 . A method of determining whether a molecule not previously known to be a modulator of protein biosynthesis is capable of transcriptionally modulating the expression of a gene-of-interest which comprises contacting a sample which contains a predefined number of cells with a predetermined amount of a molecule to be tested, each such cell comprising DNA consisting essentially of (i) a modulatable transcriptional regulatory sequence of the gene-of-interest, (ii) a promoter of the gene-of-interest, and (iii) a reporter gene, which expresses a polypeptide capable of producing a detectable signal, coupled to, and under the control of, the promoter, under conditions such that the molecule, if capable of acting as a transcriptional modulator of the gene-of-interest, causes a measureable detectable signal to be produced by the polypeptide expressed by the reporter gene, quantitatively determining the amount of the signal produced, comparing the amount so determined with the amount of produced signal detected in the absence of any molecule being tested or upon contacting the sample with any other molecule, and thereby identifying the molecule as one which causes a change in the detectable signal produced by the polypeptide expressed by the reporter gene, and thus identifying the molecule as a molecule capable of transcriptionally modulating the expression of the gene-of-interest.
58 . A method of determining whether a molecule not previously known to be a modulator of protein biosynthesis is capable of transcriptionally modulating the expression of a gene-of-interest which comprises contacting a sample which contains a predefined number of cells with a predetermined amount of a molecule to be tested, each such cell comprising DNA consisting essentially of (i) a modulatable transcriptional regulatory sequence of the gene-of-interest, (ii) a promoter of the gene-of-interest, and (iii) a DNA sequence transcribable into mRNA coupled to and under the control of, the promoter, under conditions such that the molecule, if capable of acting as a transcriptional modulator of the gene-of-interest, causes a measureable difference in the amount of mRNA transcribed from the DNA sequence, quantitatively determining the amount of the mRNA produced, comparing the amount so determined with the amount of mRNA detected in the absence of any molecule being tested or upon contacting the sample with any other molecule, and thereby identifying the molecule as one which causes a change in the detectable mRNA amount of, and thus identifying the molecule as a molecule capable of transcriptionally modulating the expression of the gene-of-interest.
59 . A method of any of claims 57 or 58 , wherein the molecule (a) does not naturally occur in the cell, (b) specifically transcriptionally modulates expression of the gene-of-interest, and (c) binds to DNA or RNA or binds to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell, the binding of a ligand to which ligand binding domain is normally associated with a defined physiological or pathological effect.
60 . A method of any of claims 57 or 58 , wherein the sample comprises cells in monolayers.
61 . A method of any of claims 57 or 58 , wherein the sample comprises cells in suspension.
62 . A method of any of claims 57 or 58 , wherein the cells comprise human, animal, or plant cells.
63 . A method of any of claims 57 or 58 , wherein the cells are bacterial cells.
64 . A method of any of claims 57 or 58 , wherein the cells are fungal cells.
65 . A method of any of claims 57 or 58 , wherein the predefined number of cells is from about 1 to about 5×10 5 cells.
66 . A method of claim 65 , wherein the predefined number of cells is from about 2×10 2 to about 5×10 4 cells.
67 . A method of any of claims 57 or 58 , wherein the predetermined amount of the molecule to be tested is based upon the volume of the sample.
68 . A method of any of claims 57 or 58 , wherein the predetermined amount is from about 1.0 pM to about 20 μM.
69 . A method of any of claims 57 or 58 , wherein the predetermined amount is from about 10 nM to about 500 μM.
70 . A method of any of claims 57 or 58 , wherein the contacting is effected from about 1 hour to about 24 hours.
71 . A method of claim 70 , wherein the contacting is effected from about 2 to about 12 hours.
72 . A method of any of claims 57 or 58 , wherein the contacting is effected with more than one predetermined amount of the molecule to be tested.
73 . A method of any of claims 57 or 58 , wherein the molecule to be tested is a purified molecule.
74 . A method of any of claims 57 or 58 , wherein the modulatable transcriptional regulatory sequence comprises a cloned genomic regulatory sequence.
75 . A method of any of claims 57 or 58 , wherein the DNA consists essentially of more than one modulatable transcriptional regulatory sequence.
76 . A method of claim 57 , wherein the reporter gene is inserted downstream of the promoter of the gene-of-interest by homologous recombination.
77 . A method of claim 57 , wherein the reporter gene encodes a luciferase.
78 . A method of claim 57 , wherein the reporter gene encodes chloramphenicol acetyltransferase.
79 . A method of claim 57 , wherein the reporter gene encodes β glucuronidase.
80 . A method of claim 57 , wherein the reporter gene encodes β galactosidase.
81 . A method of claim 57 , wherein the reporter gene encodes neomycin phosphotransferase.
82 . A method of claim 57 , wherein the reporter gene encodes guanine xanthine phosphoribosyltransferase.
83 . A method of claim 58 , wherein mRNA is detected by quantitative polymerase chain reaction.
84 . A screening method according to any of claims 57 or 58 which comprises separately contacting each of a plurality of substantially identical samples, each sample containing a predefined number of cells under conditions such that contacting is effected with a predetermined amount of each different molecule to be tested.
85 . A screening method of claim 84 , wherein the plurality of samples comprises more that about 10 4 samples.
86 . A screening method of claim 84 , wherein the plurality of samples comprises more than about 5×10 4 samples.
87 . A method of essentially simultaneously screening molecules to determine whether the molecules are capable of transcriptionally modulating one or more genes of interest in a panel of such genes which comprises essentially simultaneously screening the molecules against each of the genes of interest according to the method of claim 84 .
88 . A screening method of any of claims 86 or 87 , wherein more that about 10 3 samples per week are contacted with different molecules.
89 . A method for transcriptionally modulating in a multicellular organism the expression of a gene-of-interest, the expression of which is associated with a defined physiological or pathological effect in the organism, which comprises administering to the organism an amount of a molecule effective to transcriptionally modulate expression of the gene and thus affect the defined physiological or pathological effect, which molecule (a) does not naturally occur in the organism, (b) specifically transcriptionally modulates expression of the gene-of-interest, and (c) binds to DNA or RNA or binds to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the organism, the binding of a ligand to which ligand binding domain is normally associated with the defined physiological or pathological effect.
90 . A method of claim 89 , wherein the multicellular organism is a human being.
91 . A method of claim 89 , wherein the multicellular organism is an animal.
92 . A method of claim 89 , wherein the multicellular organism is a plant.
93 . A method of claim 89 , wherein the defined pathological effect is a disorder and modulated expression of the gene-of-interest is associated with amelioration of the disorder.
94 . A method of claim 90 , wherein the defined pathological effect is a disorder selected from the group consisting of cancer, a hematopoietic dysfunction, diabetes, tissue inflammation, atherosclerosis, viral infections, dysfunctions of memory or learning, and dysfunctions in a cholesterol or other metabolic pathway.
95 . A method of claim 91 , wherein the defined physiological effect is growth and the organism is an animal such as a man, cow, a pig, a bird, a fish, a sheep or a horse.
96 . A method of claim 92 , wherein the defined physiological or pathological effect is an agronomically important trait.
97 . A method of claim 90 or 91 , wherein the administering comprises topical contact.
98 . A method of claim 90 or 91 , wherein the administering comprises oral, transdermal, intravenous, intramuscular or subcutaneous administration.
99 . A method of any of claims 57 , 58 , or 89 , wherein the gene-of-interest encodes a naturally occurring receptor.
100 . A method of claim 99 , wherein the receptor is a testosterone receptor.
101 . A method of claim 99 , wherein the receptor is an estrogen receptor.
102 . A method of any of claims 57 , 58 , or 89 , wherein the receptor which naturally occurs in the cell is a testosterone receptor.
103 . A method of any of claims 57 , 58 , or 89 , wherein the receptor which naturally occurs in the cell is an estrogen receptor.
104 . A method of any of claims 57 , 58 , or 89 , wherein the gene-of-interest encodes a TGF-β receptor.
105 . A method of any of claims 57 , 58 , or 89 , wherein the gene-of-interest encodes TGF-β1.
106 . A method of any of claims 57 , 58 , or 89 , wherein the gene-of-interest encodes TGF-β2.
107 . A method of any of claims 57 , 58 , or 89 , wherein the gene-of-interest encodes TGF-β3.
108 . A method of any of claims 57 , 58 , or 89 , wherein the gene-of-interest encodes an oncogene.
109 . A method of claim 108 , wherein the oncogene is the neu oncogene.
110 . A method of claim 108 , wherein the oncogene is selected from the group consisting of H-, N-, and K-ras oncogenes.
111 . A method for modulating the expression of a polypeptide by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing such polypeptide which comprises contacting the cell with an amount of a molecule effective so to transcriptionally modulate expression of the polypeptide by the cell, which molecule (a) does not naturally occur in the cell and (b) binds to DNA or RNA, or binds to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell, the binding of a ligand to which ligand binding domain is normally associated with modulating transcriptional expression of a polypeptide.
112 . A method of claim 111 , wherein the polypeptide is a homologous polypeptide.
113 . A method of claim 111 , wherein the molecule specifically transcriptionally modulates expression of the polypeptide.
114 . A method of claim 111 , wherein the polypeptide is a desired product.
115 . A method of claim 114 , wherein the desired product is a monoclonal antibody.
116 . A method of claim 111 , wherein the DNA is recombinant DNA.
117 . A method of claim 111 , wherein the cell is a animal cell.
118 . A method of claim 111 , wherein the cell is a plant cell.
119 . A method of claim 111 , wherein the cell is a bacterial cell.
120 . A method of claim 111 , wherein the cell is a fungal cell.
121 . A method of claim 111 , wherein expression of the polypeptide is associated with production of a desired product.
122 . A method of claim 121 , wherein the desired product is an antibiotic.
123 . A method of claim 121 , wherein the desired product is citric acid.
124 . A biological method for recovering a substance from a mixture containing the substance which involves contacting the mixture with cells so as to separately recover the substance, which cells (i) comprise DNA encoding, and (ii) are capable of expressing a gene product, which gene product facilitates separating the substance from the mixture so as to recover the substance from the mixture, the improvement comprising (1) treating the cells with a molecule which (a) does not naturally occur in the cell and (b) binds to DNA or RNA or binds to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell, the binding of a ligand to which ligand binding domain is normally associated with increased production of the gene product.
125 . A method of claim 124 , wherein the substance is a metal.
126 . A biological method for treating a substance with cells so as to effect a biochemical transformation by contacting the substance with cells which (i) comprises DNA encoding, and (ii) is capable of expressing a gene product which permits biochemical transformation, the improvement comprising contacting the cells with a molecule which (a) does not naturally occur in the cell and (b) binds to DNA or RNA or binds to a protein through a domain of such protein which is not a ligand binding domain of a receptor which naturally occurs in the cell, the binding of a ligand to which ligand binding domain is normally associated with enhanced production of the gene product.
127 . A method of claim 126 , wherein the biochemical transformation is associated with the production of a steroid.
128 . A method of claim 126 , wherein the biochemical transformation is associated with the production of an alcohol.
129 . A method of claim 126 , wherein the biochemical transformation is associated with the degradation of petroleum products.
130 . A method for enhancing the expression of human growth hormone by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, human growth hormone, comprising contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of human growth hormone by the cell.
131 . A method for enhancing the expression of human growth hormone by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of human growth hormone by the cell.
132 . A method for enhancing the expression of human growth hormone by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, human growth hormone, comprising contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of human growth hormone by the cell.
133 . A method for enhancing the expression of human growth hormone by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, human growth hormone, comprising contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of human growth hormone by the cell.
134 . A method for enhancing the expression of human growth hormone by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, human growth hormone, comprising contacting the cell with an amount of a molecule having the structure:
wherein R is
effective to enhance the expression of human growth hormone by the cell.
135 . A method for enhancing the expression of G-CSF by a cell which (i) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of G-CSF by the cell.
136 . A method for enhancing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of molecule having the structure:
effective to enhance the expression of G-CSF by the cell.
137 . A method for enhancing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of G-CSF by the cell.
138 . A method for enhancing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of G-CSF by the cell.
139 . A method for enhancing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
wherein R1 is hydrogen or a lower alkyl group,
wherein R2 is hydrogen or a lower alkyl group,
wherein X is oxygen or —NH 2 ,
wherein Y is bromine, fluorine, chlorine, or iodine, and
which molecule is effective to enhance the expression of G-CSF by the cell.
140 . A method for enhancing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of G-CSF by the cell.
141 . A method for enhancing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of G-CSF by the cell.
142 . A method for enhancing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of G-CSF by the cell.
143 . A method for enhancing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to enhance the expression of G-CSF by the cell.
144 . A method of decreasing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to decrease the expression of G-CSF by the human being.
145 . A method of suppressing the proliferation of a mammary tumor virus in a subject who (i) comprises DNA encoding, and (ii) is capable of expressing, a mammary tumor virus, comprising administering to the subject an amount of a molecule having the structure:
115 effective to suppress the proliferation of a mammary tumor virus in the subject.
146 . A method for decreasing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to decrease the expression of G-CSF by the human being.
147 . A method of decreasing the formation of neutrophils and affecting the metabolic functions of neutrophils in a human being who (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising administering to the human being an amount of a molecule having the structure:
effective to decrease expression of G-CSF by, and thus decrease the formation and effect the metabolic functions of neutrophils in, the human being.
148 . A method of decreasing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to decrease the expression of G-CSF by the human being.
149 . A method of decreasing the formation of neutrophils and affecting the metabolic functions of neutrophils in a human being who (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising administering to the human being an amount of a molecule having the structure:
effective to decrease expression of G-CSF by, and thus decrease the formation and effect the metabolic functions of neutrophils in, the human being.
150 . A method of decreasing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to decrease the expression of G-CSF by the human being.
151 . A method of decreasing the formation of neutrophils and affecting the metabolic functions of neutrophils in a human being who (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising administering to the human being an amount of a molecule having the structure:
effective to decrease expression of G-CSF by, and thus decrease the formation and effect the metabolic functions of neutrophils in, the human being.
152 . A method of decreasing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to decrease the expression of G-CSF by the human being.
153 . A method of decreasing the formation of neutrophils and affecting the metabolic functions of neutrophils in a human being who (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising administering to the human being an amount of a molecule having the structure:
effective to decrease expression of G-CSF by, and thus decrease the formation and effect the metabolic functions of neutrophils in, the human being.
154 . A method of decreasing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to decrease the expression of G-CSF by the human being.
155 . A method of decreasing the formation of neutrophils and affecting the metabolic functions of neutrophils in a human being who (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising administering to the human being an amount of a molecule having the structure:
effective to decrease expression of G-CSF by, and thus decrease the formation and effect the metabolic functions of neutrophils in, the human being.
156 . A method of decreasing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to decrease the expression of G-CSF by the human being.
157 . A method of decreasing the formation of neutrophils and affecting the metabolic functions of neutrophils in a human being who (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising administering to the human being an amount of a molecule having the structure:
effective to decrease expression of G-CSF by, and thus decrease the formation and effect the metabolic functions of neutrophils in, the human being.
158 . A method of decreasing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to decrease the expression of G-CSF by the human being.
159 . A method of decreasing the formation of neutrophils and affecting the metabolic functions of neutrophils in a human being who (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising administering to the human being an amount of a molecule having the structure:
effective to decrease expression of G-CSF by, and thus decrease the formation and effect the metabolic functions of neutrophils in, the human being.
160 . A method of decreasing the expression of G-CSF by a cell which (i) comprises DNA encoding, and (ii) is capable of expressing, G-CSF, comprising contacting the cell with an amount of a molecule having the structure:
effective to decrease the expression of G-CSF by the human being.Join the waitlist — get patent alerts
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