N(epsilon)-(Carboxymethyl)lysine (CML), a major product of oxidative modification glycated proteins, has been suggested to represent general marker stress and long-term damage proteins in aging, atherosclerosis, diabetes. To investigate the occurrence distribution CML humans an antiserum specifically recognizing protein-bound was generated. The formation from reduced by lipoic acid, aminoguanidine, superoxide dismutase, catalase, particularly vitamin E desferrioxamine. Immunolocalization...

Background Efficient gene transfer is a major challenge for non-viral therapy. Understanding how vectors initiate expression could lead to the development of new future with enhanced efficacy. Methods Linear or branched polyethylenimine (PEI)/DNA complexes were generated in varying salt conditions and their transfection efficiencies compared vitro vivo using reporter genes, luciferase green fluorescent protein, rhodamine labeled DNA (pGeneGrip™). Results The efficiency linear PEI22/DNA was...

The process by which viruses destabilize endosomal membranes in an acidification-dependent manner has been mimicked with synthetic peptides that are able to disrupt liposomes, erythrocytes, or endosomes of cultured cells. Peptides containing the 20 amino-terminal amino acid sequence influenza virus hemagglutinin as well acidic derivatives showed erythrocyte lysis activity only when were elongated amphipathic helix carboxyl-terminal dimerization. Interestingly, consisting 23 acids also active...

Complexes containing plasmid DNA, transferrin-polylysine conjugates, and polylysine-conjugated peptides derived from the N-terminal sequence of influenza virus hemagglutinin subunit HA-2 have been used for transfer luciferase or beta-galactosidase marker genes to K562 cells, HeLa BNL CL.2 hepatocytes. These DNA complexes mimic entry viruses into as they contain functions (i) packaging nucleic acid with polylysine, (ii) attachment cell receptor-mediated endocytosis transferrin a ligand, (iii)...

We have developed a high-efficiency nucleic acid delivery system that uses receptor-mediated endocytosis to carry DNA macromolecules into cells. accomplished this by conjugating the iron-transport protein transferrin polycations bind acids. Human transferrin, as well chicken homologue conalbumin, has been covalently linked small DNA-binding protamine or polylysines of various sizes through disulfide linkage. These modified molecules maintain their ability cognate receptor and mediate...

We have examined the complement-activating properties of synthetic cationic molecules and their complexes with DNA. Commonly used gene delivery vehicles include DNA polylysine various chain lengths, transferrin-polylysine, a fifth-generation poly(amidoamine) (PAMAM) dendrimer, poly(ethyleneimine), several lipids (DOTAP, DC-Chol/DOPE, DOGS/DOPE, DOTMA/DOPE). These agents activate complement system to varying extents. Strong activation is seen long-chain polylysines, DOGS (half-maximal at...

We have previously described a gene delivery system based upon the receptor-mediated endocytosis of DNA complexed with transferrin-polycation conjugates. This has been found to be very effective for both internalization and expression genetic material in cells that many transferrin receptors. Upon scrutinization parameters involved this method, which we termed transferrinfection, note two important features process: polycation polycation-transferrin conjugates, as expected, serves attach...

We are developing efficient methods for gene transfer into tissue culture cells. have previously shown that coupling of a chimeric adenovirus with polylysine allowed the construction an adenovirus-polylysine-reporter-gene complex transferred transporter great efficiency HeLa now explored simpler, biochemical means to DNA/polylysine complexes and show such yield virtually 100% transfection in cell lines. In these is coupled polylysine, either enzymatically through action transglutaminase or...

Polymer carriers like PEI which proved their efficiency in DNA delivery were found to be far less effective for the applications with siRNA. In current study, we generated a number of nontoxic derivates branched through modification amines by ethyl acrylate, acetylation primary amines, or introduction negatively charged propionic acid succinic groups polymer structure. The resulting products showed high siRNA-mediated knockdown target gene. particular, succinylation resulted up 10-fold lower...

Abstract Background Nonviral vectors based on polyethylenimine (PEI) usually contain an excess of PEI that is not complexed to DNA. Since unbound contributes cellular and systemic toxicity, purification polyplexes from desirable. Methods Size exclusion chromatography (SEC) was used purify free PEI. Transfection properties purified the effect gene delivery were studied in vitro vivo after application into mice. Results SEC did change size zeta‐potential polyplexes. Independent amount for...

Gene transfer may be accomplished by the receptor-mediated endocytosis pathway using transferrin-polylysine conjugates. For some target cells, however, gene this vector is extremely limited, despite presence of appropriate surface receptors, a phenomenon attributed to lysosomal degradation endosome-internalized conjugate-DNA complexes. To enhance DNA escape from cell vesicle system and thus augment route, we have used capacity adenoviruses disrupt endosomes as part their entry mechanism....

Synthetic small interfering RNA (siRNA) presents an exciting novel medical opportunity. Although researchers agree that siRNA could have a great therapeutic impact, the required extracellular and intracellular delivery of these molecules into disease-associated target cells primary roadblock for broader translation medicines. Thus, design adequate technologies has utmost importance. Viruses are natural masterpieces nucleic acid present chemists drug experts with template artificial carriers...

Selective functionalization of the external surface porous nanoparticles is great interest for numerous potential applications in field nanotechnology. Regarding metal–organic frameworks (MOFs), few methods such modifications have been reported literature. Herein, we focus on covalent attachment functional polymers MIL-100(Fe) order to implement properties as increased chemical and colloidal stability or dye-labeling investigation particles by fluorescence based techniques. We prove...

Self-assembly of individual units into multicomponent complexes is a powerful approach for the generation functional superstructures. We present coordinative interaction oligohistidine-tags (His-tags) with metal-organic framework nanoparticles (MOF NPs). By this novel concept, different molecular can be anchored on outer surface MOF NPs in self-assembly process generating multifunctional nanosystems. The article focuses two main objectives: first, detailed investigation assembly and...

Carriers for RNA delivery must be dynamic, first stabilizing and protecting therapeutic during to the target tissue across cellular membrane barriers then releasing cargo in bioactive form. The chemical space of carriers ranges from small cationic lipids applied lipoplexes lipid nanoparticles, over medium-sized sequence-defined xenopeptides, macromolecular polycations polyplexes polymer micelles. This perspective highlights discovery distinct virus-inspired dynamic processes that capitalize...