Abstract
Dendritic cells are professional antigen presenting cells and are unique in their ability to prime naíve T cells. Gene modification of dendritic cells is of particular interest for immunotherapy of diseases where the immune system has failed or is aberrantly regulated, such as in cancer or autoimmune disease, respectively. Dendritic cells abundantly express mannose receptor and mannose receptor-related receptors, and receptor-mediated gene transfer via mannose receptor offers a versatile tool for targeted gene delivery into these cells. Accordingly, mannose polyethylenimine DNA transfer complexes were generated and used for gene delivery into dendritic cells. Mannose receptor belongs to the group of scavenger receptors that allow dendritic cells to take up pathogenic material, which is directed for degradation and MHC class II presentation. Therefore, a limiting step of transgene expression by mannose receptor-mediated gene delivery is endosomal degradation of DNA. Several strategies have been explored to overcome this limitation including the addition of endosomolytic components to DNA transfer complexes like adenovirus particles and influenza peptides. Here, we review the current understanding of mannose receptor-mediated gene delivery into dendritic cells and discuss strategies to identify appropriate endosomolytic agents to improve DNA transfer efficacy.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Literature Cited
Kircheis R et al. Gene Ther 1997; 4:409–418.
Wu GY, Wu CH. J Biol Chem 1987; 262:4429–4432.
Wu GY, Wu CH. J Biol Chem 1988; 263:14621–14624.
Wu CH, Wilson JM, Wu GY. J Biol Chem 1989; 264:16985–16987.
Cotten M et al. Proc Natl Acad Sci USA 1990; 87:4033–4037.
Wagner E, Zenke M, Cotten M et al. Proc Natl Acad Sci USA 1990; 87:3410–3414.
Zenke M et al. Proc Natl Acad Sci USA 1990; 87:3655–3659.
Erbacher P et al. Hum Gene Ther 1996; 7:721–729.
Ferkol T, Perales JC, Mularo F et al. Proc Natl Acad Sci USA 1996; 93:101–105.
Diebold SS, Kursa M, Wagner E et al. J Biol Chem 1999; 274:19087–19094.
Stahl P, Schlesinger PH, Sigardson E et al. Cell 1980; 19:207–215.
Stahl P, Gordon S. J Cell Biol 1982; 93:49–56.
Sallusto F, Cella M, Danieli C et al. J Exp Med 1995; 182:389–400.
Avrameas A et al. Eur J Immunol 1996; 26:394–400.
Linehan SA, Martinez-Pomares L, Stahl PD et al. J Exp Med 1999; 189:1961–1972.
Kato M et al. Int Immunol 2000; 12:1511–1519.
Jiang W et al. Nature 1995; 375:151–155.
Mahnke K et al. J Cell Biol 2000; 151:673–684.
Reise Sousa C, Stahl PD, Austyn JM. J Exp Med 1993; 178:509–519.
Diebold SS, Cotten M, Wagner E et al. Adv Exp Med Biol 1998; 451:449–455.
Diebold SS et al. Hum Gene Ther 1999; 10:775–786.
Boussif O et al. Proc Natl Acad Sci USA 1995; 92:7297–7301.
Godbey WT, Wu KK, Mikos AG. Proc Natl Acad Sci USA 1999; 96:5177–5181.
Cotten M et al. Virology 1994; 205:254–261.
Curiel DT, Agarwal S, Wagner E et al. Proc Natl Acad Sci USA 1991; 88:8850–8854.
Cotten M et al. Proc Natl Acad Sci USA 1992; 89:6094–6098.
Wagner E et al. Proc Natl Acad Sci USA 1992; 89:6099–6103.
Wagner E, Plank C, Zatloukal K et al. Proc Natl Acad Sci USA 1992; 89:7934–7938.
Plank C, Oberhauser B, Mechtler et al. J Biol Chem 1994; 269:12918–12924.
Pollard H et al. J Biol Chem 1998; 273:7507–7511.
Perales JC, Ferkol T, Molas et al. Eur J Biochem 1994; 226:255–266.
Decatur AL, Portnoy DA. Science 2000; 290:992–995.
Kawakami S, Sato A, Nishikawa M et al. Gene Ther 2000; 7:292–299.
Groger M et al. J Immunol 2000; 165:5428–5434.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Diebold, S.S., Plank, C., Cotten, M. et al. Mannose Receptor-Mediated Gene Delivery into Antigen Presenting Dendritic Cells. Somat Cell Mol Genet 27, 65–74 (2002). https://doi.org/10.1023/A:1022975705406
Issue Date:
DOI: https://doi.org/10.1023/A:1022975705406