Derivation of a triple mosaic adenovirus based on modification of the minor capsid protein IX

Virology. 2008 Aug 1;377(2):391-400. doi: 10.1016/j.virol.2008.04.023.

Abstract

Adenoviral capsid protein IX (pIX) has been shown to be a potential locale to insert targeting, imaging-related and therapeutic modalities by genetic modification. Recent evidences suggested that capsid protein mosaicism could be a promising strategy for improving the utility of Ad vector. In this study, we explored a method to genetically generate triple pIX mosaic Ad serotype 5 (Ad5) displaying three types of pIX on a single virion. pIXs were modified at their carboxy termini with a Flag sequence, a hexahistidine sequence (His(6)) or a monomeric red fluorescent protein (mRFP1), respectively. Western blotting analysis and fluorescence microscopy of the purified recombinant viruses indicated that all three modified pIXs were incorporated into the viral particles. Immuno-gold electron microscopy (EM) further confirmed that three types of pIX indeed co-existed on an individual virion. These results firstly validated a triple mosaic capsid configuration on pIX, and demonstrated the possibility of further radical design.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviruses, Human / genetics*
  • Adenoviruses, Human / physiology
  • Antigens, Viral / genetics
  • Antigens, Viral / metabolism
  • Capsid / chemistry*
  • Capsid Proteins / genetics*
  • Genetic Engineering / methods
  • Genetic Vectors
  • Microscopy, Fluorescence
  • Peptides / chemistry*
  • Peptides / genetics
  • Recombinant Fusion Proteins / metabolism
  • Virion / ultrastructure*

Substances

  • Antigens, Viral
  • Capsid Proteins
  • Peptides
  • Recombinant Fusion Proteins