Background: Several nonviral vectors including L-PEI confer a pronounced lung tropism to plasmid DNA when injected in the mouse tail vein in a non-ionic solution. Methods and Results:We have optimized this route by injecting 50 µg DNA with excess L-PEI (N/P=10) in a large volume of 5% glucose (0.4 ml). In these conditions, 1-5% percent of lung cells were transfected (corresponding to 2 ng luciferase/mg protein), the other organs remaining essentially refractory to transfection (1-10 pg luciferase/mg protein). Beta-galactosidase histochemistry confirmed alveolar cells, including pneumocytes, to be the main target, thus leading to the puzzling observation that the lung microvasculature must be permeable to cationic L-PEI/DNA particles of ca. 60 nm. A smaller injected volume, premixing of the complexes with autologous mouse serum, as well as removal of excess free L-PEI, all severely decreased transgene expression in the lung. Arterial or portal vein delivery did not increase transgene expression in other organs.Conclusions: These observations suggest that effective lung transfection primarily depends on the injection conditions: the large nonionic glucose bolus prevents aggregation as well as mixing of the cationic complexes and excess free L-PEI with blood. This may favour vascular leakage in the region where the vasculature is dense and fragile, i.e. around the lung alveoli. Cationic particles thus can reach the epithelium from the basolateral side where their receptors (heparan sulfate proteoglycans) are abundant.

Gastrointestinal microbiome, containing at least 100 trillion bacteria, resides in the mucosal surface of human intestine. Recent studies show that perturbations in the microbiota may influence physiology and link to a number of diseases, including colon tumorigenesis. Colorectal cancer (CRC), the third most common cancer, is the disease resulting from multi-genes and multi-factors, but the mechanistic details between gut microenvironment and CRC remain poorly characterized. Thanks to new technologies such as metagenome sequencing, progress in large-scale analysis of the genetic and metabolic profile of gut microbial has been possible, which has facilitated studies about microbiota composition, taxonomic alterations and host interactions. Different bacterial species and their metabolites play critical roles in the development of CRC. Also, microbiota is important in the inflammatory response and immune processes deregulation during the development and progression of CRC. This review summarizes current studies regarding the association between gastrointestinal microbiota and the development of CRC, which provides insights into the therapeutic strategy of CRC.

Background The ideal non-viral vector should be cell-type directed and form complexes with DNA that are physically stable, small and electrically neutral.