An all-feline retroviral packaging system for transduction of human cells

Hum Gene Ther. 2010 Aug;21(8):1019-27. doi: 10.1089/hum.2010.032.

Abstract

Abstract The subgroup C feline leukemia virus (FeLV-C) receptor FLVCR is a widely expressed 12-transmembrane domain transporter that exports cytoplasmic heme and is a promising target for retrovirus-mediated gene delivery. Previous studies demonstrated that FeLV-C pseudotype vectors were more efficient at targeting human hematopoietic stem cells than those pseudotyped with gibbon ape leukemia virus (GALV), and thus we developed an all FeLV-C-based packaging system, termed CatPac. CatPac is helper-virus free and can produce higher titer vectors than existing gammaretroviral packaging systems, including systems mixing Moloney murine leukemia virus (MoMLV) Gag-Pol and FeLV-C Env proteins. The vectors can be readily concentrated (>30-fold), refrozen (three to five times), and held on ice (>2 days) with little loss of titer. Furthermore, we demonstrate that CatPac pseudotype vectors efficiently target early CD34(+)CD38(-) stem/progenitor cells, monocytic and erythroid progenitors, activated T cells, mature macrophages, and cancer cell lines, suggesting utility for human cell and cell line transduction and possibly gene therapy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Antigens, CD34 / genetics
  • Antigens, CD34 / metabolism
  • Cats
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors
  • Hematopoietic Stem Cells / metabolism
  • Humans
  • Leukemia Virus, Feline / genetics*
  • Membrane Transport Proteins / genetics*
  • Receptors, Virus / genetics*
  • Transduction, Genetic*

Substances

  • Antigens, CD34
  • FLVCR1 protein, human
  • Membrane Transport Proteins
  • Receptors, Virus