Premium
A Precise Chemical Strategy To Alter the Receptor Specificity of the Adeno‐Associated Virus
Author(s) -
Kelemen Rachel E.,
Mukherjee Raja,
Cao Xiaofu,
Erickson Sarah B.,
Zheng Yunan,
Chatterjee Abhishek
Publication year - 2016
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.201604067
Subject(s) - capsid , retargeting , tropism , adeno associated virus , virus , receptor , microbiology and biotechnology , chemistry , peptide , amino acid , biology , virology , computational biology , biochemistry , vector (molecular biology) , gene , recombinant dna , computer science , computer vision
The ability to target the adeno‐associated virus (AAV) to specific types of cells, by altering the cell‐surface receptor it binds, is desirable to generate safe and efficient therapeutic vectors. Chemical attachment of receptor‐targeting agents onto the AAV capsid holds potential to alter its tropism, but is limited by the lack of site specificity of available conjugation strategies. The development of an AAV production platform is reported that enables incorporation of unnatural amino acids (UAAs) into specific sites on the virus capsid. Incorporation of an azido‐UAA enabled site‐specific attachment of a cyclic‐RGD peptide onto the capsid, retargeting the virus to the α v β 3 integrin receptors, which are overexpressed in tumor vasculature. Retargeting ability was site‐dependent, underscoring the importance of achieving site‐selective capsid modification. This work provides a general chemical approach to introduce various receptor binding agents onto the AAV capsid with site selectivity to generate optimized vectors with engineered infectivity.