Polymers for DNA delivery.
Nucleic acid delivery has many applications in basic science, biotechnology, agriculture, and medicine. One of the main applications is DNA or RNA delivery for gene therapy purposes. Gene therapy, an approach for treatment or prevention of diseases associated with defective gene expression, involves the insertion of a therapeutic gene into cells, followed by expression and production of the required proteins. This approach enables replacement of damaged genes or expression inhibition of undesired genes. Following two decades of research, there are two major methods for delivery of genes. The first method, considered the dominant approach, utilizes viral vectors and is generally an efficient tool of transfection. Attempts, however, to resolve drawbacks related with viral vectors (e.g., high risk of mutagenicity, immunogenicity, low production yield, limited gene size, etc.), led to the development of an alternative method, which makes use of non-viral vectors. This review describes non-viral gene delivery vectors, termed "self-assembled" systems, and are based on cationic molecules, which form spontaneous complexes with negatively charged nucleic acids. It introduces the most important cationic polymers used for gene delivery. A transition from in vitro to in vivo gene delivery is also presented, with an emphasis on the obstacles to achieve successful transfection in vivo.
Eliyahu
H
H
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, Jerusalem, Israel.
Barenholz
Y
Y
Domb
A J
AJ
D000818:Animals; D002478:Cells, Cultured; D004247:DNA / Q000008:administration & dosage; D050091:Dendrimers / Q000737:chemistry / Q000494:pharmacology; D018014:Gene Transfer Techniques / Q000009:adverse effects; D005822:Genetic Vectors / Q000737:chemistry; D006801:Humans; D008055:Lipids / Q000737:chemistry / Q000494:pharmacology; D008954:Models, Biological; D011094:Polyethyleneimine / Q000737:chemistry / Q000494:pharmacology; D011107:Polylysine / Q000737:chemistry / Q000494:pharmacology; D011108:Polymers / Q000737:chemistry* / Q000494:pharmacology*; D011134:Polysaccharides / Q000737:chemistry; D014780:Viruses / Q000235:genetics
D050091:Dendrimers; D008055:Lipids; D011108:Polymers; D011134:Polysaccharides; D011107:Polylysine; D011094:Polyethyleneimine; D004247:DNA