| pubmed-article:20736929 | rdf:type | pubmed:Citation | lld:pubmed |
| pubmed-article:20736929 | lifeskim:mentions | umls-concept:C0319124 | lld:lifeskim |
| pubmed-article:20736929 | lifeskim:mentions | umls-concept:C0008533 | lld:lifeskim |
| pubmed-article:20736929 | lifeskim:mentions | umls-concept:C0041485 | lld:lifeskim |
| pubmed-article:20736929 | lifeskim:mentions | umls-concept:C1160185 | lld:lifeskim |
| pubmed-article:20736929 | lifeskim:mentions | umls-concept:C0439064 | lld:lifeskim |
| pubmed-article:20736929 | lifeskim:mentions | umls-concept:C1947976 | lld:lifeskim |
| pubmed-article:20736929 | lifeskim:mentions | umls-concept:C0442335 | lld:lifeskim |
| pubmed-article:20736929 | lifeskim:mentions | umls-concept:C0591833 | lld:lifeskim |
| pubmed-article:20736929 | pubmed:issue | 12 | lld:pubmed |
| pubmed-article:20736929 | pubmed:dateCreated | 2010-12-1 | lld:pubmed |
| pubmed-article:20736929 | pubmed:abstractText | Elimination of specific surface-exposed single tyrosine (Y) residues substantially improves hepatic gene transfer with adeno-associated virus type 2 (AAV2) vectors. Here, combinations of mutations in the seven potentially relevant Y residues were evaluated for further augmentation of transduction efficiency. These mutant capsids packaged viral genomes to similar titers and retained infectivity. A triple-mutant (Y444+500+730F) vector consistently had the highest level of in vivo gene transfer to murine hepatocytes, approximately threefold more efficient than the best single-mutants, and ~30-80-fold higher compared with the wild-type (WT) AAV2 capsids. Improvement of gene transfer was similar for both single-stranded AAV (ssAAV) and self-complementary AAV (scAAV) vectors, indicating that these effects are independent of viral second-strand DNA synthesis. Furthermore, Y730F and triple-mutant vectors provided a long-term therapeutic and tolerogenic expression of human factor IX (hF.IX) in hemophilia B (HB) mice after administration of a vector dose that only results in subtherapeutic and transient expression with WT AAV2 encapsidated vectors. In summary, introduction of multiple tyrosine-mutations into the AAV2 capsid results in vectors that yield at least 30-fold improvement of transgene expression, thereby lowering the required therapeutic dose and potentially vector-related immunogenicity. Such vectors should be attractive for treatment of hemophilia and other genetic diseases. | lld:pubmed |
| pubmed-article:20736929 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:grant | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:language | eng | lld:pubmed |
| pubmed-article:20736929 | pubmed:journal | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:citationSubset | IM | lld:pubmed |
| pubmed-article:20736929 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:chemical | http://linkedlifedata.com/r... | lld:pubmed |
| pubmed-article:20736929 | pubmed:status | MEDLINE | lld:pubmed |
| pubmed-article:20736929 | pubmed:month | Dec | lld:pubmed |
| pubmed-article:20736929 | pubmed:issn | 1525-0024 | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:ZhongLiL | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:ChenLingL | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:ZolotukhinSer... | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:HerzogRoland... | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:ZolotukhinIre... | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:SrivastavaAru... | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:HoffmanBrad... | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:LiBaozhengB | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:MarkusicDavid... | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:JayandharanGi... | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:MaWenqinW | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:LiMengxinM | lld:pubmed |
| pubmed-article:20736929 | pubmed:author | pubmed-author:AslanidiGeorg... | lld:pubmed |
| pubmed-article:20736929 | pubmed:issnType | Electronic | lld:pubmed |
| pubmed-article:20736929 | pubmed:volume | 18 | lld:pubmed |
| pubmed-article:20736929 | pubmed:owner | NLM | lld:pubmed |
| pubmed-article:20736929 | pubmed:authorsComplete | Y | lld:pubmed |
| pubmed-article:20736929 | pubmed:pagination | 2048-56 | lld:pubmed |
| pubmed-article:20736929 | pubmed:dateRevised | 2011-10-4 | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:meshHeading | pubmed-meshheading:20736929... | lld:pubmed |
| pubmed-article:20736929 | pubmed:year | 2010 | lld:pubmed |
| pubmed-article:20736929 | pubmed:articleTitle | High-efficiency transduction and correction of murine hemophilia B using AAV2 vectors devoid of multiple surface-exposed tyrosines. | lld:pubmed |
| pubmed-article:20736929 | pubmed:affiliation | Division of Cellular and Molecular Therapy, Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida 32611, USA. | lld:pubmed |
| pubmed-article:20736929 | pubmed:publicationType | Journal Article | lld:pubmed |
| pubmed-article:20736929 | pubmed:publicationType | Research Support, Non-U.S. Gov't | lld:pubmed |
| pubmed-article:20736929 | pubmed:publicationType | Research Support, N.I.H., Extramural | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:20736929 | lld:pubmed |
| http://linkedlifedata.com/r... | pubmed:referesTo | pubmed-article:20736929 | lld:pubmed |
