Site-Specific Post-translational Surface Modification of Adeno-Associated Virus Vectors Using Leucine Zippers
| Autor: | Nicole N. Thadani, Joanna Yang, Ciaran M. Lee, Buhle Moyo, Gang Bao, Junghae Suh, Maria Y. Chen |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0106 biological sciences
Leucine zipper viruses Genetic Vectors Biomedical Engineering CHO Cells Gene delivery medicine.disease_cause 01 natural sciences Biochemistry Genetics and Molecular Biology (miscellaneous) Virus Article 03 medical and health sciences Capsid Cricetulus Transduction Genetic 010608 biotechnology medicine Human Umbilical Vein Endothelial Cells Animals Humans Histidine Vector (molecular biology) Gene Adeno-associated virus 030304 developmental biology 0303 health sciences Leucine Zippers Chemistry General Medicine Protein engineering Dependovirus Recombinant Proteins Cell biology Capsid Proteins Genetic Engineering Protein Processing Post-Translational |
| Zdroj: | ACS Synth Biol |
| Popis: | Adeno-associated virus (AAV) is widely favored as a gene therapy vector, tested in over 200 clinical trials internationally. To improve targeted delivery a variety of genetic capsid modifications, such as insertion of targeting proteins/peptides into the capsid shell, have been explored with some success but larger insertions often have unpredictable deleterious impacts on capsid formation and gene delivery. Here, we demonstrate a modular platform for the integration of exogenous peptides and proteins onto the AAV capsid post-translationally while preserving vector functionality. We decorated the AAV capsid with leucine-zipper coiled-coil binding motifs that exhibit specific noncovalent heterodimerization. AAV capsids successfully display hexahistidine tagged-peptides using this approach, as demonstrated through nickel column affinity. This protein display platform may facilitate the incorporation of biological moieties on the AAV surface, expanding possibilities for vector enhancement and engineering. |
| Databáze: | OpenAIRE |
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