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New nucleic acid sequences of human endogenous retrovirus, HERV-7q, used for diagnosis, treatment and prevention of autoimmune and neurological diseases

机译:人类内源性逆转录病毒HERV-7q的新核酸序列,用于诊断,治疗和预防自身免疫性疾病和神经疾病

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.
机译:纯化的核酸片段(I)包含全部或部分内源性人类逆转录病毒序列(A),包含至少一个env型基序,并且具有2599 bp的序列(1;已复制)或至少80%同源的序列在env型结构域中与(1)超过190个核苷酸(nt)或至少70%的同源性超过600 nt。还包括以下方面的独立权利要求:(1)(I)的片段(Ia),或其(反向)互补序列,或来自编码区的片段,其对应于至少14 nt的“滑动”阅读框,或其补(2)(I)或(Ia)的成绩单; (3)用于差异检测包含逆转录病毒基序的(部分)内源人类序列的诊断试剂,所述逆转录病毒基序包含(I)或其片段或(反向)补体,或能够定义或鉴定(I)或其片段或侧翼或重叠序列的核酸或它们的补语(全部可选地标记); (4)嵌合序列,其包含:(i)基因组序列的转录本和cDNA中的侧翼序列中的17-40 nt片段,该基因组序列编码(部分)与功能,(去)调节或改变相关的因子HERV-7q家族基序的正常表达或病理表达(或(去调控))(这些序列代表存在于HERV-7q两侧的侧翼区域中的基因,其中在超过120 kb的距离内未发现一端) ; (ii)17-40 nt的内源性逆转录病毒HERV-7q基序; (5)检测和/或评估内源性HERV-7q和/或其侧翼序列的过表达或过表达或修饰; (6)用于检测和/或评估自身免疫疾病的试剂盒,其包含(c)的试剂(A)和(d)中定义的基因组序列的转录本或cDNA(B); (7)由(I),(Ia)或它们的转录本编码的翻译产物(III); (8)由(1)表达的肽(IIIa)或其片段; (9)免疫原或疫苗,其除载体外还包含至少一种肽(IV),该肽(IV)含有至少一种对HLA(人类白细胞抗原)单倍型具有亲和力的CKS基序和/或至少一种基序一级或二级系统; (10)针对至少一种(IV)的抗体(Ab); (11)药物组合物,其含有针对约50种指定的肽或其类似物的中和抗体。 (12)通过比较从生物样品中提取的序列与(III)和(IIIa)的序列,鉴定或检测在癌症或神经系统疾病中异常表达的逆转录病毒基序; (13)(I),(Ia)的片段的杂合核酸或其转录物,与内源性或外源性或外源性诱导的一些其他序列或基序结合; (14)含有(I),(Ia)或其转录物的重组克隆或表达载体; (15)免疫原或疫苗,其包含载体,该载体包含至少一个编码约50种指定肽中的任一种的序列,任选地还包含CKS-17基序; (16)包含全部或部分HERV-7q序列的基因治疗载体; (17)转基因动物,其含有至少一部分HERV-7q序列。

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