Abstract:
:The inherited deficiency in adenosine deaminase (ADA), which results in severe combined immunodeficiency, is generally regarded as an optimal model for the development of human somatic gene therapy. The ideal target for the correction of ADA deficiency and other lympho-hematopoietic disorders would be the hematopoietic stem cell. We have used a combination of recombinant human interleukins-3 and -6 to stimulate the proliferation of primitive human hematopoietic progenitor cells during a period of co-cultivation with irradiated cells producing high titers of an ADA-transducing retroviral vector packaged in amphotropic particles. In a series of nine experiments, an average of 83% of the clonogenic progenitors (CFU-E and CFU-GM) were found to have acquired the transferred sequence as determined by polymerase chain reaction analysis. In addition, in two experiments, 24-44% of the clonogenic progenitors derived from long-term myeloid cultures 9 weeks post-transduction were found to contain vector sequence. The latter cells are derived from so-called "long-term culture-initiating cells" (LTC-IC), which are primitive cells probably related to hematopoietic stem cells. Moreover, the transduced ADA enzyme was found to be expressed in both normal and ADA-deficient erythroid colonies, and in the nonadherent cells of long-term bone marrow culture for at least 2 weeks at levels that approximate the endogenous ADA levels of normal erythroid cells. These results indicate that the ADA coding sequence can efficiently be introduced by retroviral gene transfer into both committed and primitive human hematopoietic progenitor cells, and that this will result in adequate expression of the transduced enzyme in the progeny of committed hematopoietic progenitors.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Cournoyer D,Scarpa M,Mitani K,Moore KA,Markowitz D,Bank A,Belmont JW,Caskey CTdoi
10.1089/hum.1991.2.3-203subject
Has Abstractpub_date
1991-10-01 00:00:00pages
203-13issue
3eissn
1043-0342issn
1557-7422journal_volume
2pub_type
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journal_title:Human gene therapy
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doi:10.1089/hum.1998.9.18-2717
更新日期:1998-12-10 00:00:00
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pub_type: 杂志文章
doi:10.1089/hum.1993.4.1-17
更新日期:1993-02-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1997.8.1-1
更新日期:1997-01-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2006.167
更新日期:2007-09-01 00:00:00
abstract::Gene transfer of reporter genes may trigger immune responses against the heterologous protein resulting in shortening of gene expression and inflammation. We generated transgenic rats expressing the lacZ gene under the control of the human immunodeficiency virus type 1 (HIV-1) long-terminal repeat (LTR) (HIV-lacZ) to ...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303402760128603
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abstract::Interleukin (IL)-12 has been reported to induce cellular immune responses for protection against tumor formation. Here we investigate the utility of adenoviral delivery of IL-12 as an adjuvant for a human papillomavirus E7 subunit vaccine in a mouse tumor challenge model. Direct intratumoral injection of AdIL-12 resul...
journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403769211619
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journal_title:Human gene therapy
pub_type: 临床试验,杂志文章
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pub_type: 杂志文章,多中心研究
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章,评审
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更新日期:2016-06-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
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journal_title:Human gene therapy
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更新日期:2006-03-01 00:00:00
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journal_title:Human gene therapy
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journal_title:Human gene therapy
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pub_type: 杂志文章
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journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:2007-01-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
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