DEGylation Enhanced the Stability of Peptide-siRNA Complexes in Serum.

Small interfering RNA (siRNA) shows great therapeutic potential due to its ability to regulate gene expression in a highly selective manner, but this application has been limited by effective delivery, partly because of the low nuclease resistance of siRNA in the presence of serum, and inefficient cellular uptake. We previously reported a library of cell-penetrating and amino acid-pairing peptides that facilitate effective siRNA delivery to mammalian cells without causing cytotoxicity, but they are unstable within serum-containing medium. Here, we investigated the possibility of conjugating the peptide with diethylene glycol to improve its serum stability without compromising its gene-regulation capability.

In vitro and in vivo therapeutic siRNA delivery induced by a tryptophan-rich endosomolytic peptide.

At the forefront of medicine, gene therapy provides an effective way to treat a range of diseases by regulating defective genes at the root of the disease. Short interfering RNAs (siRNAs) hold great promise as therapeutic agents in this domain; however, intracellular delivery remains a major obstacle to clinical applications of therapeutic siRNAs. Here we report a peptide designed to mediate siRNA delivery.

Thermodynamic investigation of the binding of dissymmetric pyrenyl-gemini surfactants to DNA.

Gemini surfactants have demonstrated significant potential for use in constructing non-viral transfection vectors for the delivery of genes into cells to induce protein expression. Previously, two asymmetric gemini surfactants containing pyrenyl groups in one of the alkyl tails of the surfactants were synthesized as fluorescence probes for use in mechanistic studies of the transfection process. Here we present the results of a thermodynamic investigation of the binding interaction(s) between the pyrenyl-modified surfactants and DNA.

A novel synthetic cannabinoid derivative inhibits inflammatory liver damage via negative cytokine regulation.

The therapeutic potential of cannabinoids has been described previously for several inflammatory diseases, but the molecular mechanisms underlying the anti-inflammatory properties of cannabinoids are not well understood. In this study, we investigated the mechanism of action of a novel synthetic cannabinoid, [(+)(6aS,10aS)-6,6-Dimethyl-3-(1,1-dimethylheptyl)-1-hydroxy-9-(1H-imidazol-2-ylsulfanylmethyl]-6a,7,10,10a-tetrahydro-6H-dibenzo[b,d]pyran (PRS-211,092) that has no psychotropic effects but exhibits immunomodulatory properties. Treatment with PRS-211,092 significantly decreased Concanavalin A-induced liver injury in mice that was accompanied by: 1) promotion of early gene expression of interleukin (IL)-6 and IL-10 that play a protective role in this model; 2) induction of early gene expression of the suppressors of cytokine signaling (SOCS-1 and 3), followed by 3) inhibition of several pro-inflammatory mediators, including IL-2, monocyte chemoattractant protein-1 (MCP-1), IL-1beta, interferon-gamma, and tumor necrosis factor alpha.