Authors: E. Soto and G. Ostroff
Affilation: University of Massachusetts Medical School, United States
Pages: 378 - 381
Keywords: targeted gene delivery, transient gene expression, DNA nanoplexes
The efficiency of non-viral gene delivery is dependent on 4 factors: DNA protection, DNA delivery across membranes, endosomal DNA release, and nuclear uptake. Here we report on the development of a new delivery technology based on the in situ layer by layer synthesis of DNA nanoplexes within hollow yeast cell wall particles (YCWP). YCWP provides protection and facilitates oral and systemic receptor-targeted delivery of DNA payloads to phagocytic cells and tissues containing these cells. Using DNA encoding green fluorescent protein (GFP) as a model system we have evaluated nanomaterials capable of overcoming these membrane hurdles. Outer nanomaterial layers have been identified that protect the DNA payload and enhance endosomal DNA release. Low levels of polyethylenimine, cationic surfactants and cationic peptides have proven effective. Inner nanomoaterial layers have been synthesized with components designed to promote DNA decomplexation and nuclear uptake to maximize transfection efficiency. Cationic peptides with nuclear localization sequences have shown the most promise. The YCWP delivery system is effective at delivering DNA and transfecting macrophages and dendritic cells in vitro and in vivo, and is currently being used in preclinical studies to orally and systemically deliver genes for vaccines and transient gene therapy of a range of diseases.