A Novel Fusion of IL-10 Engineered to Traffic across Intestinal Epithelium to Treat Colitis.

IL-10 is a potent anti-inflammatory cytokine capable of suppressing a number of proinflammatory signals associated with intestinal inflammatory diseases, such as ulcerative colitis and Crohn's disease. Clinical use of human IL-10 (hIL-10) has been limited by anemia and thrombocytopenia following systemic injection, side effects that might be eliminated by a gut-restricted distribution. We have identified a transcytosis pathway used by cholix, an exotoxin secreted by nonpandemic forms of the intestinal pathogen A nontoxic fragment of the first 386 aa of cholix was genetically fused to hIL-10 to produce recombinant AMT-101.

Membrane Association Transforms an Inert Anti-TCRβ Fab' Ligand into a Potent T Cell Receptor Agonist.

The natural peptide-major histocompatibility complex (pMHC) ligand for T cell receptors (TCRs) is inactive from solution yet capable of activating T cells at single-molecule levels when membrane-associated. This distinctive feature stems from the mechanism of TCR activation, which is thought to involve steric phosphatase exclusion as well as direct mechanical forces. It is possible to defeat this mechanism and activate T cells with solution ligands by cross-linking pMHC or using multivalent antibodies to TCR.

Extension of in vivo half-life of biologically active molecules by XTEN protein polymers.

XTEN™ is a class of unstructured hydrophilic, biodegradable protein polymers designed to increase the half-lives of therapeutic peptides and proteins. XTEN polymers and XTEN fusion proteins are typically expressed in Escherichia coli and purified by conventional protein chromatography as monodisperse polypeptides of exact length and sequence. Unstructured XTEN polypeptides have hydrodynamic volumes significantly larger than typical globular proteins of similar mass, thus imparting a bulking effect to the therapeutic payloads attached to them.

DNA-mediated assembly of protein heterodimers on membrane surfaces.

We present a method based on self-assembling oligonucleotides to anchor proteins to a supported membrane surface. This anchoring method allows control of the surface density of multiple proteins. By incorporating additional recognition sequences into the DNA linkers, defined heterodimers can be produced upon the addition of a heterospecific DNA cross-linking strand.

Controlled integration of gold nanoparticles and organic fluorophores using synthetically modified MS2 viral capsids.

The placement of fluorophores in close proximity to metal nanoparticle surfaces is proposed to enhance several photophysical properties of the dyes, potentially leading to improved quantum yields and decreased photobleaching. It is difficult in practice, however, to establish and maintain the nanoscale distances that are required to maximize these effects. The type of metal, size, and shape of the nanoparticle, the physical distance separating the metal nanoparticle from the organic dye, and the spectral properties of the fluorophore itself are all proposed to influence the quantum yield and lifetime.

Supported membranes embedded with fixed arrays of gold nanoparticles.

We present a supported membrane platform consisting of a fluid lipid bilayer membrane embedded with a fixed array of gold nanoparticles. The system is realized by preforming a hexagonal array of gold nanoparticles (∼5-7 nm) with controlled spacing (∼50-150 nm) fixed to a silica or glass substrate by block copolymer lithography. Subsequently, a supported membrane is assembled over the intervening bare substrate.

Grade III radial collateral ligament injuries of the thumb metacarpophalangeal joint: treatment by soft tissue advancement and bony reattachment.

Purpose: The purpose of this study is to report the results of intact radial collateral ligament (RCL) soft tissue sleeve advancement with bony reattachment without additional soft tissue reinforcement as the sole surgical repair technique for the treatment of grade III RCL injuries to the thumb metacarpophalangeal (MCP) joint in acute, chronic, and late cases.

Methods: During a 20-year period, 38 of 45 patients (84%) with grade III RCL injuries were found to have tears at or adjacent to the metacarpal head (25 patients) or the proximal phalanx (13 patients) and underwent surgical repair at a mean of 10.8 months after injury.

Staged flexor tendon reconstruction fingertip to palm.

Thirty-five fingertip to palm staged flexor tendon reconstructions were performed between 1971 and 1998. Tendon injuries involved 5 avulsions and 30 lacerations, 9 of which had failed primary tenorrhaphies. Follow-up evaluation averaged 30 months.