pubmed-article:21245849 | rdf:type | pubmed:Citation | lld:pubmed |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C1412056 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C0086418 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C1705338 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C1136102 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C0231441 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C0036043 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C0678812 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C1366464 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C0679058 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C0449943 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C0086022 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C1547699 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C2700640 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C0443252 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C1705099 | lld:lifeskim |
pubmed-article:21245849 | lifeskim:mentions | umls-concept:C0442335 | lld:lifeskim |
pubmed-article:21245849 | pubmed:issue | 5 | lld:pubmed |
pubmed-article:21245849 | pubmed:dateCreated | 2011-5-2 | lld:pubmed |
pubmed-article:21245849 | pubmed:abstractText | Adeno-associated virus vectors (AAV) show promise for liver-targeted gene therapy. In this study, we examined the long-term consequences of a single intravenous administration of a self-complementary AAV vector (scAAV2/ 8-LP1-hFIXco) encoding a codon optimized human factor IX (hFIX) gene in 24 nonhuman primates (NHPs). A dose-response relationship between vector titer and transgene expression was observed. Peak hFIX expression following the highest dose of vector (2 × 10(12) pcr-vector genomes (vg)/kg) was 21 ± 3 µg/ml (~420% of normal). Fluorescent in-situ hybridization demonstrated scAAV provirus in almost 100% of hepatocytes at that dose. No perturbations of clinical or laboratory parameters were noted and vector genomes were cleared from bodily fluids by 10 days. Macaques transduced with 2 × 10(11) pcr-vg/kg were followed for the longest period (~5 years), during which time expression of hFIX remained >10% of normal level, despite a gradual decline in transgene copy number and the proportion of transduced hepatocytes. All macaques developed serotype-specific antibodies but no capsid-specific cytotoxic T lymphocytes were detected. The liver was preferentially transduced with 300-fold more proviral copies than extrahepatic tissues. Long-term biochemical, ultrasound imaging, and histologic follow-up of this large cohort of NHP revealed no toxicity. These data support further evaluation of this vector in hemophilia B patients. | lld:pubmed |
pubmed-article:21245849 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21245849 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21245849 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21245849 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21245849 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21245849 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21245849 | pubmed:commentsCorrections | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21245849 | pubmed:language | eng | lld:pubmed |
pubmed-article:21245849 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21245849 | pubmed:citationSubset | IM | lld:pubmed |
pubmed-article:21245849 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21245849 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
pubmed-article:21245849 | pubmed:status | MEDLINE | lld:pubmed |
pubmed-article:21245849 | pubmed:month | May | lld:pubmed |
pubmed-article:21245849 | pubmed:issn | 1525-0024 | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:BronsonRoderi... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:DonahueRobert... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:ColemanJohnJ | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:WaddingtonSim... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:NathwaniAmit... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:NienhuisArthu... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:GrayJohn TJT | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:HighKatherine... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:DavidoffAndre... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:NgCatherine... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:ZhouJunfangJ | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:RosalesCecili... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:McCarvilleM... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:MingozziFeder... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:JacksonScottS | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:McIntoshJenny... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:SpenceYunyuY | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:SleepSusanS | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:RajDeepakD | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:ValentineMarc... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:RastegarlariG... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:NathwaniDevhr... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:NawatheSushmi... | lld:pubmed |
pubmed-article:21245849 | pubmed:author | pubmed-author:AllayJamesJ | lld:pubmed |
pubmed-article:21245849 | pubmed:issnType | Electronic | lld:pubmed |
pubmed-article:21245849 | pubmed:volume | 19 | lld:pubmed |
pubmed-article:21245849 | pubmed:owner | NLM | lld:pubmed |
pubmed-article:21245849 | pubmed:authorsComplete | Y | lld:pubmed |
pubmed-article:21245849 | pubmed:pagination | 876-85 | lld:pubmed |
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pubmed-article:21245849 | pubmed:year | 2011 | lld:pubmed |
pubmed-article:21245849 | pubmed:articleTitle | Long-term safety and efficacy following systemic administration of a self-complementary AAV vector encoding human FIX pseudotyped with serotype 5 and 8 capsid proteins. | lld:pubmed |
pubmed-article:21245849 | pubmed:affiliation | Department of Hematology, University College London Cancer Institute, London, UK. a.nathwani@ucl.ac.uk | lld:pubmed |
pubmed-article:21245849 | pubmed:publicationType | Journal Article | lld:pubmed |
pubmed-article:21245849 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
pubmed-article:21245849 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:21245849 | lld:pubmed |