Abstract:
:Dystrophic epidermolysis bullosa (DEB) comprises a family of inherited blistering skin disorders for which no corrective therapy currently exists. In the most severe form, the Hallopeau-Siemens subtype (RDEB-HS), the epidermal adhesion protein collagen VII is absent from the skin as a consequence of null mutations in the COL7A1 gene. In order to develop an ex vivo gene therapy approach for DEB, we aimed to restore expression of intact procollagen VII in RDEB-HS keratinocytes. The entire human COL7A1 locus in a P1-derived artificial chromosome (PAC) was transferred to RDEB-HS keratinocytes by microinjection, after which sustained biosynthesis and secretion of procollagen VII was detected for 1 year in vitro. Protein chemical analysis demonstrated that the chain composition, domain structure, N-glycosylation and protein folding of the newly produced procollagen VII were similar, if not identical, to its authentic counterpart, indicating that transgenic procollagen VII was structurally normal. These data demonstrate a "proof of principle" for genomic DNA vectors as a means of restoring collagen VII production in RDEB-HS skin and help develop future gene therapy protocols.
journal_name
Hum Gene Therjournal_title
Human gene therapyauthors
Mecklenbeck S,Compton SH,Mejía JE,Cervini R,Hovnanian A,Bruckner-Tuderman L,Barrandon Ydoi
10.1089/10430340260201743keywords:
subject
Has Abstractpub_date
2002-09-01 00:00:00pages
1655-62issue
13eissn
1043-0342issn
1557-7422journal_volume
13pub_type
杂志文章abstract::Reporter gene-based molecular imaging can provide invaluable information on the fate of cellular therapies postimplantation. Integrating lentiviral vectors (ILVs) are commonly used for stably engineering cells; however, their potential for insertional mutagenesis poses a significant safety concern and barrier to wides...
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journal_title:Human gene therapy
pub_type: 杂志文章
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pub_type: 临床试验,杂志文章
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journal_title:Human gene therapy
pub_type: 临床试验,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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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/hum.2007.153
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journal_title:Human gene therapy
pub_type: 杂志文章,评审
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.1995.6.4-429
更新日期:1995-04-01 00:00:00
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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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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/10430340050083298
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journal_title:Human gene therapy
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:2017-05-01 00:00:00
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/104303403765701187
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journal_title:Human gene therapy
pub_type: 临床试验,杂志文章,随机对照试验
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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
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journal_title:Human gene therapy
pub_type: 杂志文章
doi:10.1089/hum.2011.207
更新日期:2012-07-01 00:00:00