کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
3424328 1594261 2012 10 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20
موضوعات مرتبط
علوم زیستی و بیوفناوری ایمنی شناسی و میکروب شناسی ویروس شناسی
پیش نمایش صفحه اول مقاله
Structure of adeno-associated virus-2 in complex with neutralizing monoclonal antibody A20
چکیده انگلیسی

The use of adeno-associated virus (AAV) as a gene therapy vector is limited by the host neutralizing immune response. The cryo-electron microscopy (EM) structure at 8.5 Å resolution is determined for a complex of AAV-2 with the Fab’ fragment of monoclonal antibody (MAb) A20, the most extensively characterized AAV MAb. The binding footprint is determined through fitting the cryo-EM reconstruction with a homology model following sequencing of the variable domain, and provides a structural basis for integrating diverse prior epitope mappings. The footprint extends from the previously implicated plateau to the side of the spike, and into the conserved canyon, covering a larger area than anticipated. Comparison with structures of binding and non-binding serotypes indicates that recognition depends on a combination of subtle serotype-specific features. Separation of the neutralizing epitope from the heparan sulfate cell attachment site encourages attempts to develop immune-resistant vectors that can still bind to target cells.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Virology - Volume 431, Issues 1–2, 15–30 September 2012, Pages 40–49
نویسندگان
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