| Title | Site-Specific PEGylated Adeno-Associated Viruses with Increased Serum Stability and Reduced Immunogenicity |
| Authors | Yao, Tianzhuo Zhou, Xueying Zhang, Chuanling Yu, Xiaojuan Tian, Zhenyu Zhang, Lihe Zhou, Demin |
| Affiliation | Peking Univ, Sch Pharmaceut Sci, State Key Lab Nat & Biomimet Drugs, Beijing 100191, Peoples R China. |
| Keywords | adeno-associated virus 2 PEGylation genetic code expansion selective conjugation HUMAN GENE-THERAPY VIRAL VECTORS NEUTRALIZING ANTIBODIES DELIVERY LIVER MICE EXPRESSION RESPONSES MONKEYS TROPISM |
| Issue Date | 2017 |
| Publisher | MOLECULES |
| Citation | MOLECULES.2017,22(7). |
| Abstract | Adeno-associated virus (AAV) is one of the most extensively studied and utilized viral vectors in clinical gene transfer research. However, the serum instability and immunogenicity of AAV vectors significantly limit their application. Here, we endeavored to overcome these limitations by developing a straightforward approach for site-specific PEGylation of AAV via genetic code expansion. This technique includes incorporation of the azide moiety into the AAV capsid protein followed by orthogonal and stoichiometric conjugation of a variety of polyethylene glycols (PEGs) through click chemistry. Using this approach, only the chosen site(s) was consistently PEGylated under mild conditions, preventing nonselective conjugation. Upon a series of in vitro examinations, AAVs conjugated with 20-kD PEG at sites Q325+1, S452+1, and R585+1 showed a 1.7-to 2.4-fold stability improvement in pooled human serum and a nearly twofold reduction in antibody recognition. Subsequent animal research on Sprague Dawley rats displayed a promising 20% reduction in antibody inducement and a higher virus titer in the blood. Together, our data demonstrate successful protection of an AAV vector from antibody neutralization and blood clearance, thereby increasing the efficiency of therapeutic gene delivery. |
| URI | http://hdl.handle.net/20.500.11897/472326 |
| ISSN | 1420-3049 |
| DOI | 10.3390/molecules22071155 |
| Indexed | SCI(E) |
| Appears in Collections: | 药学院 天然药物与仿生药物国家重点实验室 |
