Activation of antigen-presenting cells by DNA delivery vectors.
Gene-based modulation of immune functions is a promising means of eliciting protective immunity and induction of tolerance. Novel viral and non-viral DNA delivery systems are being investigated to achieve efficient gene transfer into mammalian cells. Antigen-presenting cells (APCs), in particular dendritic cells, are crucial targets in this context due to their capacity to initiate and direct effector functions. The increasing relevance of APCs as targets of DNA vectors calls for an assessment of vector-driven activation of these cells. For viral vectors, a putative pathway of APC activation would be Toll-like receptor signalling for certain RNA genome viruses. On the other hand, non-viral vectors appear to mature APCs by interaction of polymeric particulates or bioactive lipids with cellular mechanisms. The rational design of DNA-based therapies is possible only when the intrinsic effects of the vector and immune modulation originating from the DNA are delineated. This paper will summarise recent reports of adjuvant properties of viral and non-viral delivery systems.
Meng
Wilson S
WS
Duquesne University, Division of Pharmaceutical Sciences, 600 Forbes Ave, Pittsburgh, PA 15282, USA. meng@duq.edu
Butterfield
Lisa H
LH
D000818:Animals; D000938:Antigen-Presenting Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D001672:Biocompatible Materials / Q000494:pharmacology; D004247:DNA / Q000008:administration & dosage*; D003713:Dendritic Cells / Q000187:drug effects / Q000276:immunology / Q000502:physiology; D004337:Drug Carriers / Q000494:pharmacology; D006801:Humans; D019344:Lactic Acid / Q000494:pharmacology; D011100:Polyglycolic Acid / Q000494:pharmacology; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011108:Polymers / Q000494:pharmacology; D014775:Virus Activation / Q000187:drug effects / Q000235:genetics*
D001672:Biocompatible Materials; D004337:Drug Carriers; D011108:Polymers; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D004247:DNA