title: Specific Targeting of Proerythroblasts and Erythroleukemic Cells by the VP1u Region of Parvovirus B19.
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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern , 3012 Bern, Switzerland.
authors.forename: Remo
authors.initials: R
authors.lastname: Leisi
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern , 3012 Bern, Switzerland.
authors.forename: Marcus
authors.initials: M
authors.lastname: von Nordheim
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern , 3012 Bern, Switzerland.|CSL Behring AG , 3014 Bern, Switzerland.
authors.forename: Christoph
authors.initials: C
authors.lastname: Kempf
authors.affiliation: Department of Chemistry and Biochemistry, University of Bern , 3012 Bern, Switzerland.|CSL Behring AG , 3014 Bern, Switzerland.
authors.forename: Carlos
authors.initials: C
authors.lastname: Ros
mesh_terms: D001360:Avidin / Q000378:metabolism; D001692:Biological Transport; D036022:Capsid Proteins / Q000737:chemistry / Q000378:metabolism*; D045744:Cell Line, Tumor; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism*; D004900:Erythroblasts / Q000378:metabolism*; D006801:Humans; D004915:Leukemia, Erythroblastic, Acute / Q000473:pathology*; D008958:Models, Molecular; D009841:Oligonucleotides / Q000378:metabolism; D016732:Parvovirus B19, Human; D011487:Protein Conformation
chemical_list: D036022:Capsid Proteins; D004337:Drug Carriers; D009841:Oligonucleotides; C095547:capsid protein VP1, parvovirus B19; C093483:neutravidin; D001360:Avidin