Polymer-mediated gene delivery

The first reports of using cationic polymers for DNA delivery can be traced back to 1973, before the use of cationic lipids. However, until recently, research in the area of polymer-mediated gene delivery lagged behind that of lipid-based delivery vectors [26]. Recent advances in the development of polymers have regenerated the interest in polymer-mediated gene delivery. Polycationic carriers are either naturally occurring or chemically synthesized compounds. Examples include his-... 

The plasma membrane presents cationic polymers with a substantial barrier to successfully gaining entry to the cell, as it is a dynamic and a relatively lipophilic structure that restricts the admittance of large, hydrophilic or charged molecules. The contribution of certain pathways in the uptake of cationic polymer-mediated gene delivery is not well understood it is generally believed that the uptake of polyplexes predominantly oecurs through endocytosis, although multiple mechanisms for endocytosis have been described to date and the current question is which pathway of endocytosis is responsible for cationic polymer uptake. 

Many of the early studies on polymer-mediated gene delivery employed commercially available poljuners. As they were not designed for gene delivery, their efficacy as delivery vectors is somewhat serendipitous. Off-the-shelf poisoners have nonetheless been very widely studied and form the basis for much of the gene delivery polymer literature. However, significant problems face these polymers, most... 

The structure of cationic lipids and polymers is readily amenable to chemical modification [35, 36] allowing the exploration of a virtually unlimited number of combinations and strategies at the mercy of chemists creative abilities. Various reviews have been focused on cationic lipids, dendrimers and polymers in terms of their chemical structures and their transfection properties [36—41], in an attempt to shed some light on the chemical requirements necessary to mediate gene delivery. The focus of this chapter will be to explore these carriers from a synthetic perspective, with a description of the chemical strategies used for the preparation via synthetic organic chemistry (excluding polymer synthesis) of cationic lipids and dendrimers. 

Haider, M., Leung, V., Ferrari, F. et al. (2005) Molecular engineering of silk-elastin-like polymers for matrix-mediated gene delivery Biosynthesis and characterization. Molecular Pharmaceutics, 2, 139-150. 

Scaffold-mediated gene delivery. Plasmid DNA condensed with cationic polymers can be encapsulated into various types of 3D polymeric scaffold systems (micro/nanospheres, porous sponges, or hydrogels) for sustained gene delivery. Source Reprinted and adapted from Reyes etal., 2013, copyright 2013, with permission from Elsevier B.V.)... 

The transferrin receptor was one of the first to be exploited for receptor-mediated gene delivery. All actively metabolising cells require iron that is internalised by the cell as a transferrin-iron complex by means of receptor mediated endocytosis. To exploit this ubiquitous and efficient transport mechanism for introducing DNA into cells, conjugates of chicken or human transferrin with polycations (polylysine or protamine) were synthesised and used to form complexes with plasmid DNA. The number of transferrin molecules attached to each polylysine molecule varies according to the molecular weight of the polymer, but is generally around 1 transferrin molecule for every 50 lysine residues. ... 

Yuba E, Kojima C, Sakaguchi N, Harada A, Koiwai K, Kono K (2008) Gene delivery to dendritic cells mediated by complexes of lipoplexes and pH-sensitive fusogenic polymer-modified liposomes. J Control Release 130 77-83... 

Bragonzi, B., Boletta, A., Biffi, A., et al. (1999). Comparison between cationic polymers and lipids in mediating systemic gene delivery to the lungs. Gene Then, 6, 1995-2004. 

Efficient gene delivery can also be mediated by chemically programmed polymers responding to artificial physical stimuli like heat. Depending on the stimulus, they have the ability to alter their conformation in so far as transfection enhancing effects are initiated. 

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