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FAMILY OF NUCLEIC SEQUENCES AND DEDUCTED PROTEIN SEQUENCES WITH HUMAN ENDOGENOUS RETROVIRAL PATTERNS AND THEIR APPLICATIONS
FAMILY OF NUCLEIC SEQUENCES AND DEDUCTED PROTEIN SEQUENCES WITH HUMAN ENDOGENOUS RETROVIRAL PATTERNS AND THEIR APPLICATIONS
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机译:具有人类内源性逆转录病毒模式的核酸序列和推导的蛋白质序列家族及其应用
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摘要
Purified nucleic acid fragment (I) comprises all or part of an endogenous human retroviral sequence (A), containing at least one env type motif, and either has a sequence of 2599 bp (1; reproduced) or a sequence at least 80% homologous with (1) over more than 190 nucleotides (nt) or at least 70% homologous over more than 600 nt in the env-type domains. Independent claims are also included for the following: (1) segment (Ia) of (I), or their (reverse) complements, or fragments from coding regions that correspond to a 'sliding' reading frame of at least 14 nt, or their complements; (2) transcripts from (I) or (Ia); (3) diagnostic reagent for differential detection of (partial) endogenous human sequences containing retroviral motifs comprising (I) or its fragment or (reverse) complements, or nucleic acids able to define or identify (I) or its fragments or flanking or overlapping sequences, or their complements, all optionally labeled; (4) chimeric sequences containing: (i) a 17-40 nt fragment from a flanking sequence in the transcripts and cDNA of genomic sequences that encode (part of) a factor for which the function, (de)regulation or alteration is associated with normal or pathological expression (or (de)regulation) of HERV-7q family motifs (these sequences represent genes present in the flanking regions on either side of HERV-7q, in which one end is not found at a distance of over 120 kb); and (ii) an endogenous retroviral HERV-7q motif of 17-40 nt; (5) detecting and/or evaluating under- or over-expression, or modification, of endogenous HERV-7q and/or its flanking sequences; (6) kit for detecting and/or evaluating autoimmune diseases containing the reagents (A) of (c) and transcripts or cDNA (B) of genomic sequences as defined in (d); (7) translation products (III) encoded by (I), (Ia) or their transcripts; (8) peptide (IIIa) expressed by (1) or its fragments; (9) immunogen or vaccine containing, apart from a vehicle, at least one peptide (IV) containing at least one CKS motif and/or at least one motif of a peptide that has affinity for a haplotype of the HLA (human leucocyte antigen) Class I or II systems; (10) antibodies (Ab) against at least one (IV); (11) pharmaceutical composition containing neutralizing Ab against about 50 specified peptides or their anaolgs; (12) identifying or detecting retroviral motifs that are abnormally expressed in cancer or neurological disease by comparing sequences extracted from a biological sample with sequences of (III) and (IIIa); (13) hybrid nucleic acids of a segment of (I), (Ia) or their transcripts combined with some other sequence or motif that is endogenous or exogenous, or is induced exogenously; (14) recombinant cloning or expression vector containing (I), (Ia) or their transcripts; (15) immunogen or vaccine containing a vector that includes at least one sequence encoding any of about 50 specified peptides, optionally also a CKS-17 motif; (16) gene therapy vector containing all or part of HERV-7q sequences; and (17) transgenic animal containing at least part of the HERV-7q sequence. ACTIVITY : Anticancer; anti-autoimmune disease. MECHANISM OF ACTION : Regulatory elements associated with HERV-7q may alter expression of other genes (even remote genes) on the same chromosome, inducing immunological and/or neurological changes (which may be pathological or protective/curative). Peptides derived from HERV-7q can be used to improve efficiency of the immune response, e.g. in immunotherapy.
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