Abstract:
:Although recombinant adeno-associated virus serotype 8 (AAV8) and serotype 5 (AAV5) vectors have shown efficacy in Phase 1 clinical trials for gene therapy of hemophilia B, it has become increasingly clear that these serotypes are not optimal for transducing primary human hepatocytes. We have previously reported that among the 10 most commonly used AAV serotypes, AAV serotype 3 (AAV3) vectors are the most efficient in transducing primary human hepatocytes in vitro as well as in "humanized" mice in vivo, and suggested that AAV3 vectors expressing human coagulation factor IX (hFIX) may be a more efficient alternative for clinical gene therapy of hemophilia B. In the present study, we extended these findings to develop an AAV3 vector incorporating a compact yet powerful liver-directed promoter as well as optimized hFIX cDNA sequence inserted between two AAV3 inverted terminal repeats. When packaged into an AAV3 capsid, this vector yields therapeutic levels of hFIX in hemophilia B and in "humanized" mice in vivo. Together, these studies have resulted in an AAV3 vector predicted to achieve clinical efficacy at reduced vector doses, without the need for immune-suppression, for clinical gene therapy of hemophilia B.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Brown HC,Doering CB,Herzog RW,Ling C,Markusic DM,Spencer HT,Srivastava A,Srivastava Adoi
10.1089/hum.2020.099subject
Has Abstractpub_date
2020-10-01 00:00:00pages
1114-1123issue
19-20eissn
1043-0342issn
1557-7422journal_volume
31pub_type
杂志文章abstract::Herpes simplex virus thymidine kinase (HSV-tk) gene therapy for brain tumors depends on ganciclovir (GCV) and its transport across the blood-brain tumor barrier (BBTB). We examined whether RMP-7, the bradykinin analog and potent BBTB permeabilizer, could enhance the efficacy of GCV treatment of brain tumors by increas...
journal_title:Human gene therapy
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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
doi:10.1089/hum.1996.7.1-71
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abstract::The expanding use of adenoviral vectors for gene therapy has brought about the need for new analytical tools. We have developed an anion-exchange high-performance liquid chromatography method to analyze recombinant adenovirus serotype 5 samples. Before this assay, available analytical methods consisted of either long-...
journal_title:Human gene therapy
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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.1996.7.11-1331
更新日期:1996-07-10 00:00:00
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journal_title:Human gene therapy
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doi:10.1089/104303404772679986
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journal_title:Human gene therapy
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journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2013.235
更新日期:2014-04-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050015707
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journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:2018-11-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050032401
更新日期:2000-06-10 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:1997-11-20 00:00:00
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journal_title:Human gene therapy
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更新日期:1998-12-10 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章,评审
doi:10.1089/hum.2005.16.781
更新日期:2005-07-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340150504000
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1993.4.4-433
更新日期:1993-08-01 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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journal_title:Human gene therapy
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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
doi:10.1089/104303403322542329
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journal_title:Human gene therapy
pub_type: 杂志文章
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更新日期:2011-11-01 00:00:00
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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:2013-05-01 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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journal_title:Human gene therapy
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journal_title:Human gene therapy
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