Receptor-mediated gene transfer into macrophages

Thomas Ferkol, Jose C. Perales, Frank Mularo, Richard W. Hanson

Research output: Contribution to journalArticlepeer-review

158 Scopus citations

Abstract

Gene transfer systems targeting various receptors have been developed to introduce functional genes into cells in culture and into intact animals. A synthetic molecular conjugate, consisting of mannosylated polylysine that exploits endocytosis via the macrophage mannose receptor, was constructed and complexed to expression plasmids containing either the Photinus pyralis luciferase or Escherichia coli β-galactosidase (lacZ) reporter genes. The DNA complexes were used to transfect murine macrophages isolated from peritoneal exudates in vitro. Luciferase and β-galactosidase activity was found in transfected cells in culture, whereas complexes consisting of an irrelevant plasmid bound to mannosylated polylysine or the expression plasmid bound to galactosylated polylysine resulted in no detectable transgene expression. Gene transfer was inhibited by the addition of excess mannosylated bovine serum albumin to the culture medium before transfection. Reporter genes were also transferred into macrophages residing in the spleen and liver of adult animals using this system. Luciferase activity was maximal at 4 days after transfection and decreased to lower levels by 16 days. Transgene expression conformed to the distribution of cells that had nonspecific esterase, a cytochemical marker for macrophages. Thus, this system can be used to introduce functional genes into macrophages and may be an approach to the treatment of storage diseases that affect the reticuloendothelial system.

Original languageEnglish
Pages (from-to)101-105
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number1
DOIs
StatePublished - Jan 9 1996

Keywords

  • mannose receptor
  • reticuloendothelial system
  • storage diseases

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