Current Medicinal Chemistry - Volume 11, Issue 2, 2004

Gene carriers based on lipids or polymers or a combination of these - rather than on engineered viruses - are emerging as among the “hottest technologies” for delivering genes into cells for gene therapy and therapeutics. The topic has received increasing attention having been the subject matter of recent news features in highly visible technical Magazines such as Science and Chemical & Engineering News. Indeed, as desc Read More

Cationic liposomes (CLs) are used as gene vectors (carriers) in worldwide human clinical trials of non-viral gene therapy. These lipid-gene complexes have the potential of transferring large pieces of DNA of up to 1 million base-pairs into cells. As our understanding of the mechanisms of action of CL-DNA complexes remains poor, transfection efficiencies are still low when compared to gene delivery with viral vectors. We Read More

Cationic lipid-DNA complexes, often referred to as lipoplexes, are formed spontaneously in aqueous solutions upon mixing DNA and liposomes composed of cationic and nonionic lipids. Understanding the mechanisms underlying lipoplex formation, structure and phase behavior is crucial for their further development and design as non-viral transfection vectors in gene therapy. From a physical point of view, lipoplexes are ord Read More

Cationic non-viral DNA vectors are very successful in in vitro transfections but less efficient in in vivo tests. This seems mainly due to the cationic nature of the molecules used to complex DNA. In this article, we describe the design and the route towards the realization of a non-viral non-cationic vector. The strategy follows three steps: first, the incorporation of DNA to a lamellar phase; second, the making of multilamellar Read More

Non-viral (synthetic) nucleic acid delivery systems have the potential to provide for the practical application of nucleic acid-based therapeutics. We have designed and prepared a tunable, non-viral nucleic acid delivery system that self-assembles with nucleic acids and centers around a new class of polymeric materials; namely, linear, water-soluble cyclodextrin-containing polymers. The relationships between polymer structure an Read More

Assembling structures to divide space controllably and spontaneously into subunits at the nanometer scale is a significant challenge, although one that biology has solved in two distinct ways: prokaryotes and eukaryotes. Prokaryotes have a single compartment delimited by one or more lipid-protein membranes. Eukaryotes have nested-membrane structures that provide internal compartments - such as the cell nucleus and c Read More

HIV-1 and other complex retroviruses express six auxiliary genes in addition to the canonical retroviral genes, gag, pol and env. Vif (virion infectivity factor) protein is absolutely essential for productive HIV-1 infection of peripheral blood lymphocytes and macrophages, the two major HIV-1 target cells in vivo. However, Vif is not required for production of infectious particles in several human cell lines. In spite of the prominent phen Read More

The assessment of mitochondrial respiratory chain enzyme activity in human samples is a difficult task due to both the small amount of tissue generally available and the frequent need to perform enzyme activity measurement in crude mitochondrial fraction. This is particularly true for the measurement of complex III activity which partial deficiency can be easily overlooked. In this review, we first consider the several interf Read More

α-Galactosylceramide (α-GalCer), is a glycolipid which has been identified as a ligand recognized by a special group of immune T cells, known as invariant NKT cells. γ-GalCer can powerfully activate invariant NKT cells to produce immunoregulatory cytokines, including interferon-α and IL-4, and thereby exert a variety of subsequent effects on other cells in the immune system. Recent studies have revealed the mechanism of Read More

An important virulence factor of the pathogenic fungus Cryptococcus neoformans is its polysaccharide capsule. The capsular polysaccharides glucuronoxylomannan (GXM), galactoxylomannan (GalXM) and the mannoproteins (MPs) display various immunomodulatory effects on the host response, such as the inhibition of phagocytosis, suppression of T-cell mediated immunity, and induction of immunogenic tolerance. Mor Read More