Specific Targeting of Proerythroblasts and Erythroleukemic Cells by the VP1u Region of Parvovirus B19

Bioconjug Chem. 2015 Sep 16;26(9):1923-30. doi: 10.1021/acs.bioconjchem.5b00321. Epub 2015 Aug 13.

Abstract

Viruses are evolutionarily developed cell-entering nanomachines, which are frequently used as gene or drug delivery systems. Parvovirus B19 (B19V) shows a remarkably restricted tropism for erythropoietin-dependent erythroid differentiation stages, and thus this virus provides an opportunity to deliver cargo to these intermediate differentiated cells. Here we report the construction of a delivery system from B19V subunits that maintains the highly selective cell-entry of the native virus and offers versatile cargo transport. To obtain this specific carrier, we conjugated the cell-targeting VP1u region of B19V to NeutrAvidin as a loading platform for biotinylated cargos. The VP1u-NeutrAvidin conjugate delivered fluorophores, DNA, and toxic payloads specifically to erythroid cells around the proerythroblast differentiation stage, including erythroleukemic cells. The VP1u-NeutrAvidin represents a unique cell surface marker which exclusively detects intermediate erythroid differentiation stages. Furthermore, the cell-entering property of this viral-based targeting system offers opportunities for erythroid-specific drug delivery or gene therapy.

MeSH terms

  • Avidin / metabolism
  • Biological Transport
  • Capsid Proteins / chemistry
  • Capsid Proteins / metabolism*
  • Cell Line, Tumor
  • Drug Carriers / chemistry
  • Drug Carriers / metabolism*
  • Erythroblasts / metabolism*
  • Humans
  • Leukemia, Erythroblastic, Acute / pathology*
  • Models, Molecular
  • Oligonucleotides / metabolism
  • Parvovirus B19, Human*
  • Protein Conformation

Substances

  • Capsid Proteins
  • Drug Carriers
  • Oligonucleotides
  • capsid protein VP1, parvovirus B19
  • neutravidin
  • Avidin