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Site-Specific Post-translational Surface Modification of Adeno-Associated Virus Vectors Using Leucine Zippers.
- Source :
-
ACS synthetic biology [ACS Synth Biol] 2020 Mar 20; Vol. 9 (3), pp. 461-467. Date of Electronic Publication: 2020 Feb 18. - Publication Year :
- 2020
-
Abstract
- 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.
- Subjects :
- Animals
CHO Cells
Capsid metabolism
Capsid Proteins genetics
Capsid Proteins metabolism
Cricetulus
Genetic Vectors metabolism
Histidine genetics
Human Umbilical Vein Endothelial Cells
Humans
Protein Processing, Post-Translational
Recombinant Proteins genetics
Recombinant Proteins metabolism
Transduction, Genetic
Dependovirus genetics
Genetic Engineering methods
Genetic Vectors genetics
Leucine Zippers genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2161-5063
- Volume :
- 9
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- ACS synthetic biology
- Publication Type :
- Academic Journal
- Accession number :
- 32068391
- Full Text :
- https://doi.org/10.1021/acssynbio.9b00341