Protein Transduction Into Human Cells by Adenovirus Dodecahedron Using WW Domains as Universal Adaptors

J Gene Med. 2006 Apr;8(4):524-31. doi: 10.1002/jgm.862.

Abstract

Background: Direct protein transduction is a recent technique that involves use of peptide vectors. In this study, we demonstrate that adenovirus dodecahedron (Dd), a virus-like particle devoid of DNA and able to penetrate cells with high efficiency, can be used as a vector for protein delivery.

Methods: Taking advantage of Dd interaction with structural domains called WW, we have elaborated a universal adaptor to attach a protein of interest to this vector.

Results: A tandem of three WW structural domains derived from the Nedd4 protein enables the formation of stable complexes with Dd, without impairing its endocytosis efficiency. Our protein of interest fused to the triple WW linker is delivered by the dodecahedron in 100% of cells in culture with on average more than ten million molecules per cell.

Conclusion: These data demonstrate the great potential of adenovirus dodecahedron in combination with WW domains as a protein transduction vector.

Publication types

  • Evaluation Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenoviridae / genetics*
  • Biological Transport
  • Cloning, Molecular
  • Drug Delivery Systems
  • Drug Design
  • Endosomal Sorting Complexes Required for Transport
  • HeLa Cells
  • Humans
  • Nedd4 Ubiquitin Protein Ligases
  • Peptide Fragments / therapeutic use*
  • Proteins / genetics*
  • Ubiquitin-Protein Ligases / genetics

Substances

  • Endosomal Sorting Complexes Required for Transport
  • Peptide Fragments
  • Proteins
  • Nedd4 Ubiquitin Protein Ligases
  • Nedd4 protein, human
  • Ubiquitin-Protein Ligases