Targeted mRNA Therapy for Ornithine Transcarbamylase Deficiency.

We describe a novel, two-nanoparticle mRNA delivery system and show that it is highly effective as a means of intracellular enzyme replacement therapy (i-ERT) using a murine model of ornithine transcarbamylase deficiency (OTCD). Our Hybrid mRNA Technology delivery system (HMT) comprises an inert lipid nanoparticle that protects the mRNA from nucleases in the blood as it distributes to the liver and a polymer micelle that targets hepatocytes and triggers endosomal release of mRNA. This results in high-level synthesis of the desired protein specifically in the liver.

Phage display screening of epithelial cell monolayers treated with EGTA: identification of peptide FDFWITP that modulates tight junction activity.

Phage display was used to screen for peptides that modulate the activity of epithelial cell tight junctions. Panning with a phage library that displays random 7-mers was performed using monolayers of human bronchial epithelial cells (16HBE14o(-)) treated with a calcium chelator, ethylene glycol-bis(2-aminoethylether)- N, N, N', N'-tetraacetic acid (EGTA), to increase accessibility to the junctional complex/paracellular space, followed by subtractive panning. A novel peptide, FDFWITP, identified as a potential tight junction modulator, was synthesized in linear and cyclic forms with lysine residues added to improve solubility.

Stromelysin-1 and mesothelin are differentially regulated by Wnt-5a and Wnt-1 in C57mg mouse mammary epithelial cells.

Background: The Wnt signal transduction pathway is important in a wide variety of developmental processes as well as in the genesis of human cancer. Vertebrate Wnt pathways can be functionally separated into two classes, the canonical Wnt/beta-catenin pathway and the non-canonical Wnt/Ca2+ pathway. Supporting differences in Wnt signaling, gain of function of Wnt-1 in C57mg mouse mammary epithelial cells leads to their morphological transformation while loss of function of Wnt-5a leads to the same transformation.