共查询到20条相似文献,搜索用时 15 毫秒
1.
Cavazzana-Calvo M Hacein-Bey S de Saint Basile G Gross F Yvon E Nusbaum P Selz F Hue C Certain S Casanova JL Bousso P Deist FL Fischer A 《Science (New York, N.Y.)》2000,288(5466):669-672
Severe combined immunodeficiency-X1 (SCID-X1) is an X-linked inherited disorder characterized by an early block in T and natural killer (NK) lymphocyte differentiation. This block is caused by mutations of the gene encoding the gammac cytokine receptor subunit of interleukin-2, -4, -7, -9, and -15 receptors, which participates in the delivery of growth, survival, and differentiation signals to early lymphoid progenitors. After preclinical studies, a gene therapy trial for SCID-X1 was initiated, based on the use of complementary DNA containing a defective gammac Moloney retrovirus-derived vector and ex vivo infection of CD34+ cells. After a 10-month follow-up period, gammac transgene-expressing T and NK cells were detected in two patients. T, B, and NK cell counts and function, including antigen-specific responses, were comparable to those of age-matched controls. Thus, gene therapy was able to provide full correction of disease phenotype and, hence, clinical benefit. 相似文献
2.
Prospects for human gene therapy 总被引:52,自引:0,他引:52
W F Anderson 《Science (New York, N.Y.)》1984,226(4673):401-409
Procedures have now been developed for inserting functional genes into the bone marrow of mice. The most effective delivery system at present uses retroviral-based vectors to transfer a gene into murine bone marrow cells in culture. The genetically altered bone marrow is then implanted into recipient animals. These somatic cell gene therapy techniques are becoming increasingly efficient. Their future application in humans should result in at least partial correction of a number of genetic disorders. However, the safety of the procedures must still be established by further animal studies before human clinical trials would be ethical. 相似文献
3.
Friedmann T 《Science (New York, N.Y.)》2000,287(5461):2163-2165
4.
Clonal gene therapy: transplanted mouse fibroblast clones express human alpha 1-antitrypsin gene in vivo 总被引:8,自引:0,他引:8
A retroviral vector was used to insert human alpha 1-antitrypsin (alpha 1AT) complementary DNA into the genome of mouse fibroblasts to create a clonal population of mouse fibroblasts secreting human alpha 1AT. After demonstrating that this clone of fibroblasts produced alpha 1AT after more than 100 population doublings in the absence of selection pressure, the clone was transplanted into the peritoneal cavities of nude mice. When the animals were evaluated 4 weeks later, human alpha 1AT was detected in both sera and the epithelial surface of the lungs. The transplanted clone of fibroblasts could be recovered from the peritoneal cavities of those mice and demonstrated to still be producing human alpha 1AT. Thus, even after removal of selective pressure, a single clone of retroviral vector-infected cells that expressed an exogenous gene in vitro, continued to do so in vivo, and when recovered, continued to produce the product of the exogenous gene. 相似文献
5.
Aiuti A Slavin S Aker M Ficara F Deola S Mortellaro A Morecki S Andolfi G Tabucchi A Carlucci F Marinello E Cattaneo F Vai S Servida P Miniero R Roncarolo MG Bordignon C 《Science (New York, N.Y.)》2002,296(5577):2410-2413
Hematopoietic stem cell (HSC) gene therapy for adenosine deaminase (ADA)-deficient severe combined immunodeficiency (SCID) has shown limited clinical efficacy because of the small proportion of engrafted genetically corrected HSCs. We describe an improved protocol for gene transfer into HSCs associated with nonmyeloablative conditioning. This protocol was used in two patients for whom enzyme replacement therapy was not available, which allowed the effect of gene therapy alone to be evaluated. Sustained engraftment of engineered HSCs with differentiation into multiple lineages resulted in increased lymphocyte counts, improved immune functions (including antigen-specific responses), and lower toxic metabolites. Both patients are currently at home and clinically well, with normal growth and development. These results indicate the safety and efficacy of HSC gene therapy combined with nonmyeloablative conditioning for the treatment of SCID. 相似文献
6.
Protein-DNA interactions in vivo upstream of a cell cycle-regulated human H4 histone gene 总被引:23,自引:0,他引:23
Cell cycle-dependent histone genes are transcribed at a basal level throughout the cell cycle, with a three- to fivefold increase during early S phase. Protein-DNA interactions in the 5' promoter region of a cell cycle-regulated human H4 histone gene have been analyzed at single-nucleotide resolution in vivo. This region contains two sites, with four potential protein-binding domains, at which the DNA is protected from reaction with dimethyl sulfate in cells and from digestion with deoxyribonuclease I in nuclei. These protein-DNA interactions persist during all phases of the cell cycle and dissociate with 0.16 to 0.2M sodium chloride. 相似文献
7.
A method was developed for selectively isolating genes from localized regions of the human genome that are contained in interspecific hybrid cells. Complementary human DNA was prepared from a human-rodent somatic cell hybrid that contained less than 1% human DNA, by using consensus 5' intron splice sequences as primers. These primers would select immature, unspliced messenger RNA (still retaining species-specific repeat sequences) as templates. Screening a derived complementary DNA library for human repeat sequences resulted in the isolation of human clones at the anticipated frequency with characteristics expected of exons of transcribed human genes--single copy sequences that hybridized to discrete bands on Northern (RNA) blots. 相似文献
8.
Kaiser J 《Science (New York, N.Y.)》2008,321(5893):1146-1147
9.
Qian XIAO Chang-zhi ZHAO Rui-yi LIN Guang-lei LI Chang-chun LI Hai-yan WANG Jing XU Sheng-song XIE Mei YU Shu-hong ZHAO 《农业科学学报》2019,18(5):1072-1079
Homeobox A10(Hoxa10) gene is one of the most important candidate genes associated with the reproductive performance of humans and mice. Overexpression of Hoxa10 in mouse endometrium can increase litter size. Moreover, Hoxa10 plays a key role in regulating the embryo implantation of sows. This study aimed to generate transgenic pigs using Hoxa10 via somatic cell nuclear transfer(SCNT). We established seven Hoxa10-transgenic cell lines, and two of the cell lines were selected as nuclear donors for the transfer. A total of 1 270 cloned embryos were generated and transferred to five surrogate mothers(Landrace×Yorkshire). Eight cloned male piglets were produced including one with cryptorchidism. Six transgenic piglets grew up healthy and produced 56 offspring. Finally, we obtained six transgenic male pigs and 26 transgenic positive offspring that can be used to further study the regulatory mechanism of Hoxa10 on the reproductive performance of pigs. 相似文献
10.
Minegishi Y Rohrer J Coustan-Smith E Lederman HM Pappu R Campana D Chan AC Conley ME 《Science (New York, N.Y.)》1999,286(5446):1954-1957
The signal transduction events that control the progenitor B cell (pro-B cell) to precursor B cell (pre-B cell) transition have not been well delineated. In evaluating patients with absent B cells, a male with a homozygous splice defect in the cytoplasmic adapter protein BLNK (B cell linker protein) was identified. Although this patient had normal numbers of pro-B cells, he had no pre-B cells or mature B cells, indicating that BLNK plays a critical role in orchestrating the pro-B cell to pre-B cell transition. The immune system and overall growth and development were otherwise normal in this patient, suggesting that BLNK function is highly specific. 相似文献
11.
设计5对引物P1-P5,利用PCR-SSCP技术检测227头荷斯坦母牛促破骨细胞因子1(osteoclast stimulating factor 1,OSTFl)基因部分序列的多态性.结果发现只有P3扩增的外显子7区域存在A45416G和CA5436T 2个突变位点,其中A45416G突变位点导致蛋氨酸(M)变为缬氨... 相似文献
12.
Lee E Iskow R Yang L Gokcumen O Haseley P Luquette LJ Lohr JG Harris CC Ding L Wilson RK Wheeler DA Gibbs RA Kucherlapati R Lee C Kharchenko PV Park PJ;Cancer Genome Atlas Research Network 《Science (New York, N.Y.)》2012,337(6097):967-971
Transposable elements (TEs) are abundant in the human genome, and some are capable of generating new insertions through RNA intermediates. In cancer, the disruption of cellular mechanisms that normally suppress TE activity may facilitate mutagenic retrotranspositions. We performed single-nucleotide resolution analysis of TE insertions in 43 high-coverage whole-genome sequencing data sets from five cancer types. We identified 194 high-confidence somatic TE insertions, as well as thousands of polymorphic TE insertions in matched normal genomes. Somatic insertions were present in epithelial tumors but not in blood or brain cancers. Somatic L1 insertions tend to occur in genes that are commonly mutated in cancer, disrupt the expression of the target genes, and are biased toward regions of cancer-specific DNA hypomethylation, highlighting their potential impact in tumorigenesis. 相似文献
13.
Luo J Kaplitt MG Fitzsimons HL Zuzga DS Liu Y Oshinsky ML During MJ 《Science (New York, N.Y.)》2002,298(5592):425-429
The motor abnormalities of Parkinson's disease (PD) are caused by alterations in basal ganglia network activity, including disinhibition of the subthalamic nucleus (STN), and excessive activity of the major output nuclei. Using adeno-associated viral vector-mediated somatic cell gene transfer, we expressed glutamic acid decarboxylase (GAD), the enzyme that catalyzes synthesis of the neurotransmitter GABA, in excitatory glutamatergic neurons of the STN in rats. The transduced neurons, when driven by electrical stimulation, produced mixed inhibitory responses associated with GABA release. This phenotypic shift resulted in strong neuroprotection of nigral dopamine neurons and rescue of the parkinsonian behavioral phenotype. This strategy suggests that there is plasticity between excitatory and inhibitory neurotransmission in the mammalian brain that could be exploited for therapeutic benefit. 相似文献
14.
目的:了解雄性激素受体基因( Androgen receptor gene)突变对少精不育病症发生所起的作用及突变的来源。方法:利用 P C R 对45 例精液标本和配对的血液标本 A R基因8 个外显子分别进行扩增。扩增产物经琼脂糖电泳和聚丙烯胺的 C D G E电泳分析,检测基因片段的插入和缺失及点突变。结果:45 例少精不育患者的精液标本中,外显子 A 即基因转录激活区发生点突变者3 例,插入突变4 例,缺失突变3 例共10 例,占22.2% ;外显子 H 发生缺失突变1 例、外显子 G 处发生点突变1 例、外显子 E发生完全缺失突变1 例、不完全缺失突变1 例;同时他们的血液标本中,只有3 例在外显子 A发生插入突变。结论:雄性激素受体基因外显子 A 即基因转录激活区的突变是造成少精不育的重要原因。突变一般发生在减数分裂期,少数是亲代遗传。 相似文献
15.
Chircurel M 《Science (New York, N.Y.)》2000,290(5498):1878
The emerging understanding of HIV's journey from the cell membrane to the nucleus may help researchers design better vectors for gene therapy for a variety of diseases. Researchers are using HIV itself as a gene-therapy vector, thereby capitalizing on its ability to infect nondividing cells. 相似文献
16.
为寻找与乳房炎相关的分子标记,以期为荷斯坦牛的抗病育种提供理论基础,利用PCR SSCP技术和直接测序技术对宁夏农垦303头中国荷斯坦牛的TLR6基因进行了遗传多态性分析,利用一般线性模型分析TLR6基因c.640G>A突变位点与中国荷斯坦牛体细胞评分(SCS)以及各个因素之间的相关性。结果表明,中国荷斯坦牛TLR6基因c.640G>A突变位点与SCS值和胎次之间存在极显著和显著相关性,GA和AA基因型个体的SCS值极显著低于GG基因型个体(P<001)。因此,在中国荷斯坦牛育种中,可尝试将c.640G>A突变位点的GA基因型作为低SCC/SCS牛的优良基因型加以应用。 相似文献
17.
以金花茶胚性培养物为材料,对体胚PPO基因克隆以及在体胚发生过程中的转录水平进行q PCR分析和酶活性变化检测.结果表明:克隆获得的金花茶PPO基因c DNA序列1788 bp,含有完整的开放阅读框(ORF),编码595个氨基酸;与登录Gen Bank的山茶属其他植物PPO基因序列进行核苷酸和氨基酸比对发现,同源性分别为74%和72%左右.同时,以18S rRNA作为内参基因进行的q PCR分析表明:金花茶体胚发生过程中PPO基因表达量呈下降趋势,球形胚PPO基因表达量最大,子叶胚和心形胚次之,成熟胚最小;而正常子叶胚和花状多子叶胚的表达量存在明显差异.此外,对金花茶体胚发生过程中PPO活性变化检测结果表明:在此过程中PPO活性明显比较低,变化趋势与PPO基因定量表达结果相似,推测PPO基因可能在金花茶体胚发生早期发挥重要作用. 相似文献
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19.
LMO2-associated clonal T cell proliferation in two patients after gene therapy for SCID-X1 总被引:1,自引:0,他引:1
Hacein-Bey-Abina S Von Kalle C Schmidt M McCormack MP Wulffraat N Leboulch P Lim A Osborne CS Pawliuk R Morillon E Sorensen R Forster A Fraser P Cohen JI de Saint Basile G Alexander I Wintergerst U Frebourg T Aurias A Stoppa-Lyonnet D Romana S Radford-Weiss I Gross F Valensi F Delabesse E Macintyre E Sigaux F Soulier J Leiva LE Wissler M Prinz C Rabbitts TH Le Deist F Fischer A Cavazzana-Calvo M 《Science (New York, N.Y.)》2003,302(5644):415-419
20.
本试验克隆了龙眼体胚Obg1基因(DLObg1)的3个转录本.序列分析表明,DLOBG1蛋白具有典型的OBG蛋白结构域,与其他植物的OBG蛋白具有较高的同源性,与葡萄、蓖麻和玉米的氨基酸序列同源性分别为84%、84%和82%.实时荧光定量PCR分析显示,DLObg1基因的转录水平随龙眼体胚的发育而变化,在心形胚和鱼雷形胚阶段的表达量最高,可能与子叶等器官的形成有关. 相似文献