Abstract:
:Gene transfer studies for the treatment of hemophilia began more than two decades ago. A large body of pre-clinical work evaluated a variety of vectors and target tissues, but by the start of the new millennium it became evident that adeno-associated viral (AAV)-mediated gene transfer to the liver held great promise as a therapeutic tool. The transition to the clinical arena uncovered a number of unforeseen challenges, mainly in the form of a human-specific immune response against the vector that poses a significant limitation in the application of this technology. While the full nature of this response has not been elucidated, long-term expression of therapeutic levels of factor IX is already a reality for a small number of patients. Extending this success to a greater number of hemophilia B patients remains a major goal of the field, as well as translating this strategy to clinical therapy for hemophilia A. This review summarizes the progress of AAV-mediated gene therapy for the hemophilias, along with its upcoming prospects and challenges.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
High KA,Anguela XMdoi
10.1093/hmg/ddv475subject
Has Abstractpub_date
2016-04-15 00:00:00pages
R36-41issue
R1eissn
0964-6906issn
1460-2083pii
ddv475journal_volume
25pub_type
杂志文章,评审abstract::Mitochondrial dysfunction is implicated in aging and degenerative disorders such as Parkinson's disease (PD). Continuous fission and fusion of mitochondria shapes their morphology and is essential to maintain oxidative phosphorylation. Loss-of-function mutations in PTEN-induced kinase1 (PINK1) or Parkin cause a recess...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds352
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章
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journal_title:Human molecular genetics
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doi:10.1093/hmg/ddw076
更新日期:2016-05-15 00:00:00
abstract::Mutations in the parkin gene, encoding an E3 ubiquitin-protein ligase, are a frequent cause of autosomal recessive parkinsonism and are also involved in sporadic Parkinson's disease. Loss of Parkin function is thought to compromise the polyubiquitylation and proteasomal degradation of specific substrates, leading to t...
journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/dds072
更新日期:2012-06-01 00:00:00
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2014-02-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2010-01-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddaa113
更新日期:2020-08-03 00:00:00
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journal_title:Human molecular genetics
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更新日期:2013-07-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddw197
更新日期:2016-10-01 00:00:00
abstract::Clinical, electrophysiological and genetic linkage studies were performed on a large autosomal dominant family with Charcot-Marie-Tooth axonal neuropathy type 2 (CMT2) with 38 members of which 14 were affected. Onset of the disease was between 16 and 30 years of age with weakness and atrophy of the hands more severe t...
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pub_type: 杂志文章
doi:10.1093/hmg/5.9.1373
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddt572
更新日期:2014-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/11.12.1381
更新日期:2002-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/4.5.895
更新日期:1995-05-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2010-09-01 00:00:00
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pub_type: 临床试验,杂志文章
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journal_title:Human molecular genetics
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更新日期:1996-06-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2013-05-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/5.9.1305
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journal_title:Human molecular genetics
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doi:10.1093/hmg/ddx430
更新日期:2018-02-15 00:00:00
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journal_title:Human molecular genetics
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doi:10.1093/hmg/10.26.3083
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