Current Medicinal Chemistry - Volume 10, Issue 14, 2003

Completion of the working draft of human genome has unquestionably strengthened the clinical potential of gene therapy. The principle of gene therapy is simple: “Supplement the body cells with the corrected copies of the malfunctioning genes”. However, given that both the macromolecular genes (DNA) and biological cell surfaces are negatively charged, spontaneous entry of naked DNA inside cells are unlik Read More

Successful gene therapy depends on efficient gene transfer vectors. Viral vectors and non-viral vectors have been investigated extensively. Cationic lipids are non-viral vectors, which resemble traditional pharmaceuticals, display little immunogenicity, and have no potential for viral infection. However, toxicity and low transfection efficiency are two barriers limiting the clinical applications of cationic lipids. Over the last decade, Read More

Gene therapy research is in crisis owing to the lack of acceptable vector systems to deliver nucleic acids to patients for therapy. Viral vectors are efficient but currently appear to be too dangerous for routine clinical use. Synthetic non-viral vectors are inherently much safer but are currently not efficient enough to be clinically viable. The solution for gene therapy lies with improved synthetic non-viral vectors based upon well-f Read More

Cationic liposome-DNA complexes, also called “lipoplexes”, constitute a potentially viable alternative to viral vectors for the delivery of therapeutic genes. Here we review the mechanisms of lipoplex-mediated gene delivery, the barriers to efficient gene expression, and novel cationic lipids used for transfection. We also describe methods for enhancing gene transfer via the use of proteins, including transferrin, albumin and asialo Read More

The use of an efficient carrier for nucleic acid-based medicines is considered to be a determinant factor for the successful application of gene therapy. The drawbacks associated with the use of viral vectors, namely those related with safety problems, have prompted investigators to develop alternative methods for gene delivery, cationic lipid-based systems being the most representative. Despite extensive research i Read More

Non-viral synthetic vectors for gene delivery represent a safer alternative to viral vectors. Their main drawback is the low transfection efficiency, especially in vivo. Among the non-viral vectors currently in use, the cationic liposomes composed of cationic lipids are the most common. This review discusses the physicochemical properties of cationic lipids, the formation, macrostructure and specific parameters of the corresp Read More

Among other strategies, the use of cationic lipids as autoassembling vehicles for non viral DNA transfection has received considerable attention. An exponentially growing litterature has been published on this topic (over 700 hits for the past decade, including 400 in the last two years). The present review focuses on the main present strategies aiming at improving cationic lipids induced transfection, and on some of the freq Read More

Optimization of cationic liposomal complexes for in vivo applications is complex involving many diverse components. These components include nucleic acid purification, plasmid design, formulation of the delivery vehicle, administration route and schedule, dosing, detection of gene expression, and others. This review will primarily focus on optimization of the delivery vehicle formulation. These formulation issues incl Read More

The present article reviews interesting cationic liposomes (cationic transfection lipids) with novel cationic cholesterol derivatives, a new strategy in gene transfection developed by our group and the presently accepted molecular mechanism of gene transfection. Use of confocal laser scanning microscopy and atomic force microscopy in elucidating the molecular mechanism of gene transfection by cationic liposomes is also revi Read More

The clinical success of gene therapy is critically dependent on the development of efficient and safe gene delivery reagents, popularly known as “Transfection Vectors”. The transfection vectors commonly used in gene therapy are mainly of two types: viral and non-viral. The efficiencies of viral transfection vectors are, in general, superior to their non-viral counterparts. However, the myriads of potentially adverse immunog Read More

This review focuses on the recent developments in study of cationic lipids as carriers for DNA delivery. Emphasis is placed on a class of compounds as exemplifies by their similarity in structures and transfection activities. The technical aspects are also reviewed on how to prepare DNA-lipid complexes and to perform transfection. A brief discussion of the current views on the mechanism of cationic lipid-mediated DNA transfe Read More