Oral gene delivery with chitosan–DNA nanoparticles generates immunologic protection in a murine model of peanut allergy

Abstract

Food allergy is a common and often fatal disease with no effective treatment. We describe here a new immunoprophylactic strategy using oral allergen-gene immunization to modulate peanut antigen-induced murine anaphylactic responses. Oral administration of DNA nanoparticles synthesized by complexing plasmid DNA with chitosan, a natural biocompatible polysaccharide, resulted in transduced gene expression in the intestinal epithelium. Mice receiving nanoparticles containing a dominant peanut allergen gene (pCMVArah2) produced secretory IgA and serum IgG2a. Compared with non-immunized mice or mice treated with 'naked' DNA, mice immunized with nanoparticles showed a substantial reduction in allergen-induced anaphylaxis associated with reduced levels of IgE, plasma histamine and vascular leakage. These results demonstrate that oral allergen-gene immunization with chitosan-DNA nanoparticles is effective in modulating murine anaphylactic responses, and indicate its prophylactic utility in treating food allergy.

Robust and prolonged gene expression from injectable polymeric implants

“…Pre-formed polymeric systems for gene delivery have been administered subcutaneously, 10 intravenously, 14 intramuscularly, 11,15 or orally 16,17 with promising results. These systems used various techniques to fabricate delivery systems from biodegradable polymers.…”

Chitosan as a nonviral gene delivery system. Structure–property relationships and characteristics compared with polyethylenimine in vitro and after lung administration in vivo

“…16 In a promising study (published during the course of this work), chitosan-based formulations of pDNA encoding for the reporter gene beta-galactosidase gave a significant gene expression after intestinal installation, providing evidence that chitosan may, at least under certain conditions, be an effective gene delivery system in vivo. 17 More importantly, oral administration of the chitosan formulation carrying a plasmid that encodes a peanut allergen induced tolerance against peanut allergy in a challenge model. 17 However, this study conflicts with several other investigations, which have found chitosan to be a relatively inefficient gene delivery system in vitro and in vivo.…”

“…17 More importantly, oral administration of the chitosan formulation carrying a plasmid that encodes a peanut allergen induced tolerance against peanut allergy in a challenge model. 17 However, this study conflicts with several other investigations, which have found chitosan to be a relatively inefficient gene delivery system in vitro and in vivo. 18,19 Thus, the factors that determine the effectiveness of chitosan-based gene delivery systems need to be clarified.…”

Oral Nonviral Gene Delivery for Chronic Protein Replacement Therapy

“…Recent studies suggest that flash nanocomplexation may be particularly suitable for the manufacturing of these NPs 36, 37. It has been 20 years since the first report suggesting the feasibility of using nonviral vectors to generate a therapeutic effect through oral administration 7. The ensuing years have only produced promise plagued by modest efficacy and low reproducibility.…”

“…Chitosan (CS) is an attractive gene carrier because of its low toxicity to cells7 and tunable physicochemical characteristics. Varying the molecular weight ( M W ) and degree of deacetylation (DA) of CS can yield a polysaccharide with different biodegradability and charge density at physiological pH.…”