Abstract
The development of safe and effective gene delivery methods is a major challenge to enable gene therapy or DNA vaccines to become a reality. Currently there are two major approaches for delivery of genetic material, viral and non-viral. The majority of on-going clinical trials in gene therapy or DNA vaccines use retroviruses and adenoviruses for delivering genetic materials. Viral delivery systems are far more effective than non-viral delivery however there are concerns regarding toxicity, immunogenicity and possible integration of viral genetic material into the human genome. Given the negative charge of the phosphate backbone of DNA, polycationic molecules have been the major focus as carriers of DNA. There are several physiological barriers to overcome for effective systemic delivery of DNA. The ideal vector must be stable in the systemic circulation, escape the reticuloendothelial system, able to extravasate tissues, enter the target cell, escape lysosomal degradation and transport DNA to the nucleus to be transcribed. With increasing understanding of the physicochemical properties essential to overcome the various barriers, it is possible to apply rational design to the cationic carriers. A number of poly-amino acids, cationic block co-polymers, dendrimers and cyclodextrins have been rationally designed to optimize gene delivery. This review will discuss approaches that have been used to design various synthetic polycations with enhanced DNA condensing ability, serum stability and endosomolytic capability for efficient gene transfer in vitro and in vivo.
Keywords: Polyethyleneimine, poly-L-lysine, DNA, vaccine, gene delivery
Mini-Reviews in Medicinal Chemistry
Title: Structure and Design of Polycationic Carriers For Gene Delivery
Volume: 6 Issue: 12
Author(s): Geoffrey A. Pietersz, Choon-Kit Tang and Vasso Apostolopoulos
Affiliation:
Keywords: Polyethyleneimine, poly-L-lysine, DNA, vaccine, gene delivery
Abstract: The development of safe and effective gene delivery methods is a major challenge to enable gene therapy or DNA vaccines to become a reality. Currently there are two major approaches for delivery of genetic material, viral and non-viral. The majority of on-going clinical trials in gene therapy or DNA vaccines use retroviruses and adenoviruses for delivering genetic materials. Viral delivery systems are far more effective than non-viral delivery however there are concerns regarding toxicity, immunogenicity and possible integration of viral genetic material into the human genome. Given the negative charge of the phosphate backbone of DNA, polycationic molecules have been the major focus as carriers of DNA. There are several physiological barriers to overcome for effective systemic delivery of DNA. The ideal vector must be stable in the systemic circulation, escape the reticuloendothelial system, able to extravasate tissues, enter the target cell, escape lysosomal degradation and transport DNA to the nucleus to be transcribed. With increasing understanding of the physicochemical properties essential to overcome the various barriers, it is possible to apply rational design to the cationic carriers. A number of poly-amino acids, cationic block co-polymers, dendrimers and cyclodextrins have been rationally designed to optimize gene delivery. This review will discuss approaches that have been used to design various synthetic polycations with enhanced DNA condensing ability, serum stability and endosomolytic capability for efficient gene transfer in vitro and in vivo.
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Cite this article as:
Pietersz A. Geoffrey, Tang Choon-Kit and Apostolopoulos Vasso, Structure and Design of Polycationic Carriers For Gene Delivery, Mini-Reviews in Medicinal Chemistry 2006; 6 (12) . https://dx.doi.org/10.2174/138955706778992987
DOI https://dx.doi.org/10.2174/138955706778992987 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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