ALPHA-1-ANTITRYPSIN GENE AND PULMONARY EMPHYSEMA

ALPHA-1-抗胰蛋白酶基因与肺气肿

基本信息

  • 批准号:
    3339192
  • 负责人:
  • 金额:
    $ 12.2万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    1982
  • 资助国家:
    美国
  • 起止时间:
    1982-09-01 至 1990-03-30
  • 项目状态:
    已结题

项目摘要

Alpha-1-antitrypsin is a plasma protease inhibitor that accounts for 90% of the total anti-protease activities in the blood. Reduced serum levels of this protein in certain individuals constitute a genetic disorder known as alpha-1-antitrypsin deficiency, which predisposes affected individuals to high risk of developing chronic obstructive pulmonary emphysema. The deficiency is characterized by the presence of variant alpha-1-antitrypsin of the Z or S phenotypes instead of the normal M phenotype, and is inherited by an autosomal recessive trait. Serum levels of alpha-1-antitrypsin in ZZ homozygotes and SZ heterozygotes are 12 and 35% of the normal individuals, respectively. The frequencies of the Z and S genes are such that 1/3000 to 1/4000 of caucasians in the United States are of the ZZ phenotype and 1/800 are of the SZ phenotype. It has been estimated that 80-90% of ZZ homozygotes will develop pulmonary emphysema of various severity, and there is no cure for this genetic disorder at the present time. Subtle amino acid substitutions in alpha-1-antitrypsin between the Z and S deficient phenotypes and the normal M phenotype have been reported. Since only limited amino acid sequence of the normal and variant proteins have been determined, whether there are additional amino acid substitutions between these proteins are not known at the present time. Using Recombinant DNA Technology, we propose to isolate and characterize the human Alpha-1-antitrypsin gene from normal and deficient individuals by molecular cloning. Comparison of the structural organization and nucleotide sequence between the cloned genes should reveal any additional amino acid substitutions in the variant proteins and would thereby establish the molecular basis of the deficiency at the gene level. This information will then permit the development of a simple and reliable method for prenatal diagnosis of the genetic disorder by gene mapping. Early detection of individuals with the genetic disorder will permit better management of the deficiency, which will in turn reduce the risk of their developing pulmonary emphysema later in life. Finally, attempts will be made to better understand the cause(s) of the deficiency by examining the expression of the deficient genes after their introduction through DNA mediated gene transfer into a human hepatoma cell line which synthesizes and secretes normal Alpha-1-antitrypsin.
α -1-抗胰蛋白酶是一种血浆蛋白酶抑制剂,占血浆蛋白酶的90%

项目成果

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Savio L Woo其他文献

Savio L Woo的其他文献

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{{ truncateString('Savio L Woo', 18)}}的其他基金

Anaerobic Bacteria as Oncopathic Agents for Pancreatic Cancer
厌氧细菌作为胰腺癌的致癌剂
  • 批准号:
    7651591
  • 财政年份:
    2009
  • 资助金额:
    $ 12.2万
  • 项目类别:
Phase I Clinical Translation Trial of Oncolytic rVSV-F Virotherapy for HCC
溶瘤 rVSV-F 病毒疗法治疗 HCC 的 I 期临床转化试验
  • 批准号:
    7077291
  • 财政年份:
    2006
  • 资助金额:
    $ 12.2万
  • 项目类别:
Phase I Clinical Translation Trial of Oncolytic rVSV-F Virotherapy for HCC
溶瘤 rVSV-F 病毒疗法治疗 HCC 的 I 期临床转化试验
  • 批准号:
    7667824
  • 财政年份:
    2006
  • 资助金额:
    $ 12.2万
  • 项目类别:
Phase I Clinical Translation Trial of Oncolytic rVSV-F Virotherapy for HCC
溶瘤 rVSV-F 病毒疗法治疗 HCC 的 I 期临床转化试验
  • 批准号:
    7476525
  • 财政年份:
    2006
  • 资助金额:
    $ 12.2万
  • 项目类别:
Anaerobic Bacteria as Therapeutic Agents for Metastatic Cancer
厌氧细菌作为转移性癌症的治疗剂
  • 批准号:
    7229908
  • 财政年份:
    2006
  • 资助金额:
    $ 12.2万
  • 项目类别:
Anaerobic Bacteria as Therapeutic Agents for Metastatic
厌氧细菌作为转移性治疗剂
  • 批准号:
    7025161
  • 财政年份:
    2006
  • 资助金额:
    $ 12.2万
  • 项目类别:
Phase I Clinical Translation Trial of Oncolytic rVSV-F Virotherapy for HCC
溶瘤 rVSV-F 病毒疗法治疗 HCC 的 I 期临床转化试验
  • 批准号:
    7929907
  • 财政年份:
    2006
  • 资助金额:
    $ 12.2万
  • 项目类别:
Phase I Clinical Translation Trial of Oncolytic rVSV-F Virotherapy for HCC
溶瘤 rVSV-F 病毒疗法治疗 HCC 的 I 期临床转化试验
  • 批准号:
    7276134
  • 财政年份:
    2006
  • 资助金额:
    $ 12.2万
  • 项目类别:
GROWTH, DIFFERENTIATION AND GENETIC ALTERATION OF HUMAN ES CELLS
人类 ES 细胞的生长、分化和遗传改变
  • 批准号:
    7092813
  • 财政年份:
    2005
  • 资助金额:
    $ 12.2万
  • 项目类别:
Genetic Reconstitution for Phenylketonuria
苯丙酮尿症的基因重建
  • 批准号:
    6680669
  • 财政年份:
    2003
  • 资助金额:
    $ 12.2万
  • 项目类别:

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SCGE 疾病模型研究补充:对小鼠和猪模型中改善 α-1-抗胰蛋白酶缺乏症的 Prime 编辑进行评估。
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