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.
Remo Leisi  1 ,  Marcus von Nordheim  1 ,  Christoph Kempf  1  2 ,  Carlos Ros  1  2
Affiliations
  • 1. Department of Chemistry and Biochemistry, University of Bern , 3012 Bern, Switzerland.
  • 2. CSL Behring AG , 3014 Bern, Switzerland.
PMID: 26240997 DOI: 10.1021/acs.bioconjchem.5b00321
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.

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