Journal
CURRENT PHARMACEUTICAL DESIGN
Volume 13, Issue 27, Pages 2837-2850Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/138161207781757024
Keywords
polycationic dendrimer; non-viral gene delivery; dendriplex; DNA; oligonucleotide; cell penetrating peptide; transfection; anti-body
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The quest towards achieving a better understanding of underlying mechanisms by which genetic factors contribute to human disease has gathered considerable momentum, most notably due to the drafting of the complete human genome sequence. This has in turn accelerated research into identifying genes responsible for a plethora of genetic, infectious and metabolic diseases with the vision that therapies can then be developed. Although achieving a therapeutic intervention by gene delivery is perfectly feasible, the practical approach to achieving such a goal, at least in vivo, has proved far more challenging. Employing viruses as gene vectors has to-date proven to be the most effective method of delivery however concerns have emerged about both the short and long-term risks they pose. These fears being confirmed by incidents which led to the tragic deaths of subjects believed to have been triggered by adeno- & retroviral vectors used in clinical trials. This prompted many in the field to turn their research focus towards developing non-viral vectors deemed not only to be safer (non-immunogenic) than their viral counterparts but with a greater gene loading capacity. Polycationic dendrimers (PCDs) as vectors for this purpose have attracted significant interest due to their ease of synthesis, versatility and tolerability. This review will explore the physicochemical parameters crucial to PCD-mediated gene delivery and highlight some innovative strategies designed to maximise transfection efficacy and facilitate tissue-targeting of these elaborate macromolecules:
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