Journal
JOURNAL OF DRUG TARGETING
Volume 20, Issue 4, Pages 301-328Publisher
TAYLOR & FRANCIS LTD
DOI: 10.3109/1061186X.2012.655247
Keywords
Gene delivery; non-viral; gene carriers; nucleic acid; RNAi; plasmid; sustained-release system; targeted drug delivery; transgene; Immune response
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Funding
- Natural Sciences and Engineering Research Council (NSERC)
- Canadian Institutes of Health Research (CIHR)
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The delivery of nucleic acid molecules into cells to alter physiological functions at the genetic level is a powerful approach to treat a wide range of inherited and acquired disorders. Biocompatible materials such as cationic polymers, lipids, and peptides are being explored as safer alternatives to viral gene carriers. However, the comparatively low efficiency of nonviral carriers currently hampers their translation into clinical settings. Controlling the size and stability of carrier/nucleic acid complexes is one of the primary hurdles as the physicochemical properties of the complexes can define the uptake pathways, which dictate intracellular routing, endosomal processing, and nucleocytoplasmic transport. In addition to nuclear import, subnuclear trafficking, posttranscriptional events, and immune responses can further limit transfection efficiency. Chemical moieties, reactive linkers or signal peptide have been conjugated to carriers to prevent aggregation, induce membrane destabilization and localize to subcellular compartments. Genetic elements can be inserted into the expression cassette to facilitate nuclear targeting, delimit expression to targeted tissue, and modulate transgene expression. The modular option afforded by both gene carriers and expression cassettes provides a two-tier multicomponent delivery system that can be optimized for targeted gene delivery in a variety of settings.
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