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(12) Patent Application Publication (10) Pub. No.: US 2009/00992.59 A1 Jouni Et Al

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(12) Patent Application Publication (10) Pub. No.: US 2009/00992.59 A1 Jouni Et Al US 200900992.59A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2009/00992.59 A1 Jouni et al. (43) Pub. Date: Apr. 16, 2009 (54) METHOD FOR REGULATING GENE Related U.S. Application Data EXPRESSION (60) Provisional application No. 60/777,724, filed on Feb. (76) Inventors: Zeina Jouni, Evansville, IN (US); 28, 2006. Joshua Anthony, Evansville, IN (US); Steven C. Rumsey, Curitiba Publication Classification (BR): Deshanie Rai, Evansville, IN (US); Kumar Sesha Kothapalli, (51) Int. Cl. Ithaca, NY (US); James T. Brenna, A6II 3L/20 (2006.01) Ithaca, NY (US) A6IP3/00 (2006.01) A6IP 25/00 (2006.01) Correspondence Address: A6IP37/00 (2006.01) Richard D. Schmidt Bristol-Myers Squibb Company (52) U.S. Cl. ........................................................ 514/560 2400 West Lloyd Expressay Evansville, IN 47721-0001 (US) (57) ABSTRACT (21) Appl. No.: 11/712,102 The present invention is directed to a novel method for modu lating the expression of one or more genes in a subject by (22) Filed: Feb. 28, 2007 administering an amount of DHA and ARA to the subject. ::::::: Patent Application Publication Apr. 16, 2009 US 2009/00992.59 A1 s :::::::::: US 2009/00992.59 A1 Apr. 16, 2009 METHOD FOR REGULATING GENE expression of certain genes in Subjects and thereby prevent EXPRESSION the onset of or treat various diseases and disorders. SUMMARY OF THE INVENTION 0001. This application claims the priority benefit of U.S. 0011 Briefly, the present invention is directed to a novel Provisional Application 60/777,724 filed Feb. 28, 2006 which method for modulating the expression of one or more genes in is incorporated by reference herein in its entirety. a Subject, wherein the gene is selected from the group con sisting of those genes listed in Tables 4-9 herein under the “Gene Symbol column, the method comprising administer BACKGROUND OF THE INVENTION ing to the subject DHA and ARA, alone or in combination with one another. The subject can be an infant or a child. The 0002 (1) Field of the Invention Subject can be one that is in need of Such modulation. In 0003. The present invention relates generally to a method particular situations, ARA and DHA can be administered in a for modulating gene expression in Subjects. ratio of ARA:DHA of between about 1:10 to about 10:1 by weight. 0004 (2) Description of the Related Art 0012. The present invention is also directed to a novel 0005. Every gene contains the information required to method for upregulating the expression of one or more genes make a protein or a non-coding ribonucleic acid (RNA). In in a Subject, wherein the gene is selected from the group order to produce functional RNA and protein molecules in a consisting of those genes listed in Tables 4 and 6 herein under cell, however, a gene must be expressed. Gene expression the “Gene Symbol' column, the method comprising admin occurs in two major stages, transcription and protein synthe istering to the subject DHA or ARA, alone or in combination sis. During transcription, the gene is copied to produce an with one another. RNA molecule (a primary transcript) with essentially the 0013 The present invention is additionally directed to a same sequence as the gene. Most human genes are divided novel method for downregulating the expression of one or into exons and introns, and only the exons carry information more genes in a Subject, wherein the gene is selected from the required for protein synthesis. Most primary transcripts are group consisting of those genes listed in Tables 5 and 7 under therefore processed by splicing to remove intron sequences the “Gene Symbol' column, the method comprising admin and generate a mature transcript or messenger RNA (mRNA) istering to the subject DHA or ARA, alone or in combination that only contains exons. with one another. 0014. The present invention is also directed to a novel 0006. The second stage of gene expression, protein syn method for upregulating the expression of one or more genes thesis, is also known as translation. During this stage there is in a Subject, wherein the gene is selected from the group no direct correspondence between the nucleotide sequence in consisting of TIMM8A, TIMM23, NF1, SFTPB, ACADSB, deoxyribonucleic acid (DNA) and RNA and the sequence of SOD, PDE3A, NSMAF, OSBP2, FTH1, SPTLC2, FOXP2, amino acids in the protein. In fact, three nucleotides are LUM, BRCA1, ADAM17, ADAM33, TOB1, XCL1, XCL2, required to specify one amino acid. RNASE2, RNASE3, SULT1C1, HSPCA, CD44, CD24, 0007 All genes in the human genome are not expressed in OSBPL9, FCER1G, FXD3, NRF1, STK3, and KIR2DS1, the the same manner. Some genes are expressed in all cells all of method comprising administering to the Subject DHA or the time. These so-called housekeeping genes are essential ARA, alone or in combination with one another. for very basic cellular functions. Other genes are expressed in 0015 The invention is further directed, in an embodiment, particular cell types or at particular stages of development. to a method for modulating the expression of one or more For example, the genes that encode muscle proteins such as genes in a subject, wherein the gene is selected from the group actin and myosin are expressed only in muscle cells, not in the consisting of TIMM8A, TIMM23, NF1, LUM, BRCA1, cells of the brain. Still other genes can be activated or inhib ADAM17, TOB1, RNASE2, RNASE3, NRF1, STK3, FZD3, ited by signals circulating in the body, Such as hormones. ADAM8, PERP, COL4A6, PLA2G6, MSRA, CTSD, CTSB, LMX1B, BHMT, TNNC1, PDE3A, PPARD, NPY1R, LEP, 0008. This differential gene expression is achieved by and any combination thereof. regulating transcription and translation. All genes are Sur 0016. The present invention is also, in an embodiment, rounded by DNA sequences that control their expression. directed to a method for treating or preventing tumors in a Proteins called transcription factors bind to these sequences Subject, the method comprising modulating a gene selected and can Switch the genes on or off. Gene expression is there from the group consisting of TOB1, NF1, FZD3, STK3, fore controlled by the availability and activity of different BRCA1, NRF1, PERP, and COL4A6 in the subject by admin transcription factors. istering to the subject an effective amount of DHA or ARA, 0009. As transcription factors are proteins themselves, alone or in combination with one another. they must also be produced by genes, and these genes must be 0017. The invention is directed to a method for treating or regulated by other transcription factors. In this way, all genes preventing neurodegeneration in a Subject, the method com and proteins can be linked into a regulatory hierarchy starting prising modulating a gene selected from the group consisting with the transcription factors present in the egg at the begin of PLA2G6, TIMM8A, ADAM17, TIMM23, MSRA, CTSD, ning of development. A number of human diseases are known CTSB, LMX1B, and BHMT in the subject by administering to result from the absence or malfunction of transcription to the subject an effective amount of DHA or ARA, alone or factors and the disruption of gene expression thus caused. in combination with one another. The invention is also 0010. If genes are not expressed in the right time, place and directed to a method for improving vision in a Subject, the amount, disease may occur. Thus, it would be beneficial to method comprising modulating the LUM gene in the Subject provide a composition that can regulate or modulate the by administering to the subject an effective amount of DHA US 2009/00992.59 A1 Apr. 16, 2009 or ARA, alone or incombination with one another. The inven present discussion is a description of exemplary embodi tion is further directed to a method for treating or preventing ments only, and is not intended as limiting the broader aspects macular degeneration in a Subject, the method comprising of the present invention. modulating the LUM gene in the Subject by administering to 0025. The term “modulation', as used herein, means a the subject an effective amount of DHA or ARA, alone or in positive or negative regulatory effect on the expression of a combination with one another. gene. 0.018. In other embodiments, the invention is directed to a 0026. As used herein, the term “upregulate” means a posi method for stimulating an immune response in a Subject, the tive regulatory effect on the expression of a gene. method comprising modulating a gene selected from the 0027. The term "downregulate” means a negative regula group consisting of RNASE2, RNASE3, and ADAM8 in the tory effect on the expression of a gene. Subject by administering to the Subject an effective amount of DHA or ARA, alone or in combination with one another. The 0028. As used herein the term “expression” means the invention is directed to a method for improving lung function conversion of genetic information encoded in a gene into in a subject, the method comprising modulating the ADAM33 mRNA, transfer RNA (tRNA) or ribosomal RNA (rRNA) gene in the Subject by administering to the Subject an effective through transcription. amount of DHA or ARA, alone or in combination with one 0029. The term “infant’ means a postnatal human that is another. The invention is also directed to a method for less than about 1 year of age. improving cardiac function in a subject, the method compris 0030 The term “child' means a human that is between ing modulating a gene selected from the group consisting of about 1 year and 12 years of age. In some embodiments, a TNNC1 and PDE3A in the subject by administering to the child is between the ages of about 1 and 6 years.
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