Introduction: Inhaled gene therapy of muco-obstructive lung diseases requires a strategy to achieve therapeutically relevant gene transfer to airway epithelium covered by particularly dehydrated and condensed mucus gel layer. Here, we introduce a synthetic DNA-loaded mucus-penetrating particle (DNA-MPP) capable of providing safe, widespread and robust transgene expression in in vivo and in vitro models of muco-obstructive lung diseases.
Methods: We investigated the ability of DNA-MPP to mediate reporter and/or therapeutic transgene expression in lung airways of a transgenic mouse model of muco-obstructive lung diseases (ie, -Tg) and in air-liquid interface cultures of primary human bronchial epithelial cells harvested from an individual with cystic fibrosis.
Inhaled gene therapy poses a unique potential of curing chronic lung diseases, which are currently managed primarily by symptomatic treatments. However, it has been challenging to achieve therapeutically relevant gene transfer efficacy in the lung due to the presence of numerous biological delivery barriers. Here, we introduce a simple approach that overcomes both extracellular and cellular barriers to enhance gene transfer efficacy in the lung in vivo.
View Article and Find Full Text PDFColon cancer is one of the major causes of morbidity and mortality worldwide. Dietary phytochemicals have been drawing increasing attention for colon cancer prevention and treatment due to their chemical diversity, biological activity, easy availability, lack of toxic effects, and ability to modulate various signal transduction pathways and cell processes. The chemoprotective effects elicited by phytochemicals include antioxidative and anti-inflammatory activities, induction of phase II enzymes, cell cycle arrest, apoptosis, autophagy, and changes in gut microbiota.
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