Interferon-alpha induced gene

#The present invention relates to identification of a human gene upregulated by interferon-α (IFN-α) administration, the coding sequence of which is believed to be previously unknown. Detection of expression products of this gene may find use in predicting responsiveness to IFN-α and other interferons which act at the Type 1 interferon receptor. Therapeutic use of the isolated novel protein encoded by the same gene is also envisaged.

#IFN-α is widely used for the treatment of a number of disorders. Disorders which may be treated using IFN-α include neoplastic diseases such as leukaemia, lymphomas, and solid tumours, AIDS-related Kaposi's sarcoma and viral infections such as chronic hepatitis. IFN-α has also been proposed for administration via the oromucosal route for the treatment of autoimmune, mycobacterial, neurodegenerative, parasitic and viral disease. In particular, IFN-α has been proposed, for example, for the treatment of multiple sclerosis, leprosy, tuberculosis, encephalitis, malaria, cervical cancer, genital herpes, hepatitis B and C, HIV, HPV and HSV-1 and 2. It has also been suggested for the treatment of arthritis, lupus and diabetes. Neoplastic diseases such as multiple myeloma, hairy cell leukaemia, chronic myelogenous leukaemia, low grade lymphoma, cutaneous T-cell lymphoma, carcinoid tumours, cervical cancer, sarcomas including Kaposi's sarcoma, kidney tumours, carcinomas including renal cell carcinoma, hepatic cellular carcinoma, nasopharyngeal carcinoma, haematological malignancies, colorectal cancer, glioblastoma, laryngeal papillomas, lung cancer, colon cancer, malignant melanoma and brain tumours are also suggested as being treatable by administration of IFN-α via the oromucosal route, i.e. the oral route or the nasal route.

#IFN-α is a member of the Type 1 interferon family, which exert their characteristic biological activities through interaction with the Type 1 interferon receptor. Other Type 1 interferons include IFN-β, IFN-ω and IEN-τ.

#FIG. 1: cDNA clones isolated from a BALB/C mouse spleen cDNA library were sequenced and assembled. The longest ORF is represented as the shaded area and the sequence of the band isolated by differential display is emboldened. Potential polyadenylation sites are underlined.

#FIG. 2: The amino acid sequence deduced from the mouse ORF was compared to the sequence of the human ADIR protein using the MULTALIN alignment program. Identities are boxed in black and similarities in grey. The typical motifs of ATP binding proteins, A,−B, and Box IV are indicated. Only the putative sites for phosphorylation (PKC, protein kinase C, CK2, casein kinase II; TK, tyrosine kinase) and for glycosylation (Gly) conserved in both human and mouse sequences are indicated.

#FIG. 3: Characterisation and tissue distribution of human HuIFRG46/ADIR transcripts. 1 to 14: Brain (whole brain, amygdala, caudate nucleus, cerebellum, cerebral cortex, frontal lobe, hippocampus, medulla oblongata. occipital lobe, putamen, substantia nigra, temporal lobe, thalamus, subthalamic nucleus) 15 to 20 spinal cord. heart, aorta, skeletal muscle, colon, bladder. 21 to 30 uterus, prostate, stomach, testis, ovary, pancreas, pituitary gland, adrenal gland. thyroid gland, salivary gland. 31 to 43 mammary gland, kidney, liver, small intestine, spleen, thymus, peripheral leukocyte, lymph node, bone marrow. appendix, lung, trachea, placenta. 44 to 50 fetal tissues (brain, heart, kidney, liver, spleen, thymus, lung.) Most of the tissues are pools of several individuals except for the cerebral cortex and adult liver. The fetal mRNA are pools from at least 14 embryos of ages comprised between 17 to 25 weeks. The mRNA samples dotted on the membrane have been normalized to the mRNA expression level of eight different housekeeping genes.

#SEQ. ID. No.1 is the amino acid sequence of human protein HuIFRG46/ADIR and its encoding cDNA.

#SEQ. ID. No.2 is the amino acid sequence alone of HuIFRG46/ADIR protein.

#SEQ. ID. No.3 is the amino acid sequence of a variant of human protein HuIFRG46/ADIR and its encoding cDNA.