Evaluation of transfection efficacy, biodistribution, and toxicity of branched amphiphilic peptide capsules (BAPCs) associated with mRNA.

Nanoparticles (NPs) have been shown to be a suitable mRNA delivery platform by conferring protection against ribonucleases and facilitating cellular uptake. Several NPs have succeeded in delivering mRNA intranasally, intratracheally, and intramuscularly in preclinical settings. However, intravenous mRNA delivery has been less explored.

Design of Peptides that Fold and Self-Assemble on Graphite.

The graphite-water interface provides a unique environment for polypeptides that generally favors ordered structures more than in solution. Therefore, systems consisting of designed peptides and graphitic carbon might serve as a convenient medium for controlled self-assembly of functional materials. Here, we computationally designed cyclic peptides that spontaneously fold into a β-sheet-like conformation at the graphite-water interface and self-assemble, and we subsequently observed evidence of such assembly by atomic force microscopy.

Efficacy and safety of mirogabalin for the treatment of fibromyalgia: results from three 13-week randomized, double-blind, placebo- and active-controlled, parallel-group studies and a 52-week open-label extension study.

To investigate the efficacy and safety of mirogabalin, an αδ ligand, in patients with fibromyalgia (FM). In three 13-week, multicenter, double-blind, phase 3 studies (studies A, B, and C), patients with FM ( = 1293, 1270, and 1301, respectively) were randomized (1:1:1:1) to placebo, pregabalin 150 mg twice daily, mirogabalin 15 mg once daily or mirogabalin 15 mg twice daily. The primary endpoint was the change in weekly average daily worst pain score (ADPS) at week 13.

Branched Amphipathic Peptide Capsules: Different Ratios of the Two Constituent Peptides Direct Distinct Bilayer Structures, Sizes, and DNA Transfection Efficiency.

Branched amphipathic peptide capsules (BAPCs) are biologically derived, bilayer delimited, nanovesicles capable of being coated by or encapsulating a wide variety of solutes. The vesicles and their cargos are readily taken up by cells and become localized in the perinuclear region of cells. When BAPCs are mixed with DNA, the BAPCs act as cationic nucleation centers around which DNA winds.

Symmetry breaking during homodimeric assembly activates an E3 ubiquitin ligase.

C-terminus of Hsc/p70-Interacting Protein (CHIP) is a homodimeric E3 ubiquitin ligase. Each CHIP monomer consists of a tetratricopeptide-repeat (TPR), helix-turn-helix (HH), and U-box domain. In contrast to nearly all homodimeric proteins, CHIP is asymmetric.

Organization and Structure of Branched Amphipathic Oligopeptide Bilayers.

A class of self-assembling branched amphiphilic peptide capsules (BAPCs) was recently developed that could serve as a new drug delivery vehicle. BAPCs can encapsulate solutes up to ∼12 kDa during assembly, are unusually stable, and are readily taken up by cells with low cytotoxicity. Coarse-grained simulations have supported that BAPCs are defined by bilayers that resemble those formed by diacyl phospholipids.

A review of solute encapsulating nanoparticles used as delivery systems with emphasis on branched amphipathic peptide capsules.

Various strategies are being developed to improve delivery and increase the biological half-lives of pharmacological agents. To address these issues, drug delivery technologies rely on different nano-sized molecules including: lipid vesicles, viral capsids and nano-particles. Peptides are a constituent of many of these nanomaterials and overcome some limitations associated with lipid-based or viral delivery systems, such as tune-ability, stability, specificity, inflammation, and antigenicity.

Thermally induced conformational transitions in nascent branched amphiphilic peptide capsules.

Branched amphiphilic peptide capsules (BAPCs) are biocompatible, bilayer delimited polycationic nanospheres that spontaneously form at room temperature through the coassembly of two amphiphilic branched peptides: bis(FLIVI)-K-K4 and bis(FLIVIGSII)-K-K4. BAPCs are readily taken up by cells in culture, where they escape and/or evade the endocytic pathway and accumulate in the perinuclear region, persisting there without apparent degradation or extravasation. Drugs, small proteins, and solutes as well as α particle emitting radionuclides are stably encapsulated for extended periods of time.

Branched amphiphilic peptide capsules: cellular uptake and retention of encapsulated solutes.

Branched amphiphilic peptide capsules (BAPCs) are peptide nano-spheres comprised of equimolar proportions of two branched peptide sequences bis(FLIVI)-K-KKKK and bis(FLIVIGSII)-K-KKKK that self-assemble to form bilayer delimited capsules. In two recent publications we described the lipid analogous characteristics of our BAPCs, examined their initial assembly, mode of fusion, solute encapsulation, and resizing and delineated their capability to be maintained at a specific size by storing them at 4°C. In this report we describe the stability, size limitations of encapsulation, cellular localization, retention and, bio-distribution of the BAPCs in vivo.

Branched oligopeptides form nanocapsules with lipid vesicle characteristics.

In a recent article (Gudlur et al. PLOS ONE, 2012, 7 (9) e45374), we described the special properties of a mixed branched peptide assembly in which equimolar bis(FLIVI)-K-KKKK and bis(FLIVIGSII)-K-KKKK self-associate to form bilayer delimited capsules capable of trapping solutes. These polycationic vesicle-like capsules are readily taken up by epithelial cells in culture, escape or evade the endocytic pathway, and accumulate in the perinuclear region where they persist without any apparent degradation.