Perspectives of development of the nanocarriers for delivery of genetic materials into cells

Abstract

The successful delivery of nucleic acids to particular target sites is the challenge that is being addressed using a variety of viral and non-viral delivery systems, both of which have distinct advantages and disadvantages. Non-viral vectors offer the advantage of safety and flexibility over viral vectors, although they lack efficiency. Dendrimers are novel, three dimensional polymers that have the ability to interact with various forms of nucleic acids such as plasmid DNA, antisense oligonucleotides and RNA to form complexes that protect the nucleic acid from degradation. The interaction between the dendrimers and the nucleic acids is purely electrostatic where the cationic dendrimer condenses the anionic nucleic acids. Because cell membranes are negatively charged, the net positive charge of the dendrimer nucleic acid complex determines the transfection efficiency, although highly cationic systems are also cytotoxic. The nature of the dendrimer nucleic acid complex depends on various factors like stoichiometry, concentration of dendrimer amines and nucleic acid phosphates, as well as bulk solvent properties like pH, salt concentration, buffer strength, and dynamics of mixing. This article aims to review the role of dendrimers as novel gene delivery vectors both in-vitro and in-vivo. Dendrimer based transfection reagents have become routine tools for in-vitro transfection, but in-vivo delivery of therapeutic nucleic acids remains a challenge. ______________________________________________________________________________________ INTRODUCTION Gene therapy is an approach that aims to cure inherited and acquired diseases by correcting the overexpression or under-expression of defective genes. The success of gene therapy is largely dependent upon the development of a vector that delivers and efficiently expresses a therapeutic gene in a specific cell population. Gene therapy protocols were originally designed to correct inheritable disorders, such as adenosine deaminase deficiency, cystic fibrosis, Gaucher's disease, and Duchenne muscular dystrophy. However, gene therapy has been considered more recently as a promising tool for treating acquired diseases H. M. Marvaniya et al