转导(生物物理学)
衣壳
腺相关病毒
遗传增强
生物
祖细胞
基因传递
胚胎干细胞
再生医学
转基因
诱导多能干细胞
病毒载体
细胞生物学
细胞
病毒学
分子生物学
基因
干细胞
病毒
载体(分子生物学)
遗传学
重组DNA
生物化学
作者
L Zhang,Axel Rossi,Lucas Lange,Nadja Meumann,Ulrike Koitzsch,Kathleen A. Christie,M. Andrew Nesbit,Casey Moore,Ulrich Hacker,Michael Morgan,Dirk Hoffmann,James Zengel,Jan E. Carette,Axel Schambach,Anna Salvetti,Margarete Odenthal,Hildegard Büning
出处
期刊:Human Gene Therapy
[Mary Ann Liebert]
日期:2019-10-01
卷期号:30 (10): 1284-1296
被引量:23
摘要
Endothelial cells (EC) are targets in gene therapy and regenerative medicine, but they are inefficiently transduced with adeno-associated virus (AAV) vectors of various serotypes. To identify barriers hampering efficient transduction and to develop an optimized AAV variant for EC transduction, we screened an AAV serotype 2-based peptide display library on primary human macrovascular EC. Using a new high-throughput selection and monitoring protocol, we identified a capsid variant, AAV-VEC, which outperformed the parental serotype as well as first-generation targeting vectors in EC transduction. AAV vector uptake was improved, resulting in significantly higher transgene expression levels from single-stranded vector genomes detectable within a few hours post-transduction. Notably, AAV-VEC transduced not only proliferating EC but also quiescent EC, although higher particle-per-cell ratios had to be applied. Also, induced pluripotent stem cell-derived endothelial progenitor cells, a novel tool in regenerative medicine and gene therapy, were highly susceptible toward AAV-VEC transduction. Thus, overcoming barriers by capsid engineering significantly expands the AAV tool kit for a wide range of applications targeting EC.
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