衣壳
腺相关病毒
生物
向性
群体特异性抗原
病毒学
突变体
病毒
组织向性
犬细小病毒
遗传增强
转基因
病毒载体
转导(生物物理学)
细胞生物学
基因
细小病毒
载体(分子生物学)
重组DNA
遗传学
作者
Anne Girod,Martin Ried,Christiane E. Wobus,Harald Lahm,Kristin Leike,Jürgen A. Kleinschmidt,Gilbert Deléage,Michael Hallek
出处
期刊:Nature Medicine
[Springer Nature]
日期:1999-09-01
卷期号:5 (9): 1052-1056
被引量:277
摘要
The human parvovirus adeno-associated virus type 2 (AAV2) has many features that make it attractive as a vector for gene therapy. However, the broad host range of AAV2 might represent a limitation for some applications in vivo, because recombinant AAV vector (rAAV)-mediated gene transfer would not be specific for the tissue of interest. This host range is determined by the binding of the AAV2 capsid to specific cellular receptors and/or co-receptors. The tropism of AAV2 might be changed by genetically introducing a ligand peptide into the viral capsid, thereby redirecting the binding of AAV2 to other cellular receptors. We generated six AAV2 capsid mutants by inserting a 14-amino-acid targeting peptide, L14, into six different putative loops of the AAV2 capsid protein identified by comparison with the known three-dimensional structure of canine parvovirus. All mutants were efficiently packaged. Three mutants expressed L14 on the capsid surface, and one efficiently infected wild-type AAV2-resistant cell lines that expressed the integrin receptor recognized by L14. The results demonstrate that the AAV2 capsid tolerates the insertion of a nonviral ligand sequence. This might open new perspectives for the design of targeted AAV2 vectors for human somatic gene therapy.
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