Abstract
Conventional drugs consist of a formulation of a bioactive species and a carrier, the former accounting for most of the sophistication of the design. In the case of biomolecular drugs, however, the role of the carrier becomes decisive in enabling the load to reach its target to carry out its designed therapeutic function. Thus, the clinical success of gene therapy, where the active principles are nucleic acids, critically depends on the use of efficient and safe delivery systems. Carbohydrates have proven particularly useful in this regard. Glycocoating, similarly to poly(ethylene)glycol (PEG)-coating (pegylation), can stabilize colloidal aggregates by improving solvation and preventing nonspecific interactions, for example, with serum proteins. Moreover, glycoconjugates can drive specific recognition and receptor-mediated internalization in target cells. Actually, the inherent flexibility of carbohydrate and glycoconjugate chemistry has greatly contributed to enlarging the range of functional materials that can be rationally conceived for gene delivery. Herein, this is illustrated with selected examples that focus on controlling the architectural parameters of the vectors to make them suitable for structure–activity relationship (SAR) and optimization studies. The members of the cyclomaltooligosaccharide (cyclodextrin, CD) family will be the central actors of the story.
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