Correlation between surface electric field changes of recombinant adeno-associated virus capsid protein and its serotype
10.13200/j.cnki.cjb.004686
- VernacularTitle:重组腺相关病毒衣壳蛋白表层电场变化与其血清型的相关性分析
- Author:
Meng GAO
1
Author Information
1. National Institutes for Food and Drug Control, NHC Key Laboratory of Research on Quality and Standardization of Biotech Products, NMPA Key Laboratory for Quality Research and Evaluation of Biological Products, Beijing 100050, China
- Publication Type:Journal Article
- Keywords:
Recombinant adeno-associated virus(rAAV);
Capsid protein;
Electric field changes;
Neutralizing antibodies;
Serotype changes
- From:
Chinese Journal of Biologicals
2026;39(04):506-512
- CountryChina
- Language:Chinese
-
Abstract:
Adeno-associated virus(AAV) has been widely used in the field of gene therapy due to its good safety,low immunogenicity and stable expression. It is a commonly used gene delivery and expression vector. However,AAV vectors still have problems such as poor targeting ability and host immune response,which hinder the application. The effects of mutations and modifications of amino acid residues in recombinant AAV(rAAV) capsid protein on the electric field of capsid protein,and how these effects further modulate the binding efficiency of neutralizing antibodies to the viral capsid were investigated. The Poisson distribution model was also used to estimate the interaction probability of neutralizing antibodies with the viral capsid,and the results were compared with the variations of the known AAV serotypes. It was found that the mutation or modification of a single amino acid residue on the capsid protein resulting electric field changes are not enough to completely block the binding of neutralizing antibodies. However,double or multiple mutations may bring the virus close to the brink of serotype change. In addition,the receptor compatibility of the emerging capsid type in vivo is also an important factor influencing serotype changes. This study provides a method to evaluate the association between AAV capsid protein mutations and serotypes,providing a theoretical basis for the further research and application of rAAV vectors.
