Sequence-defined nucleic acid carriers combining distinct modules for complexation, shielding, recep

来源 :The Third Symposium on Innovative Polymers for Controlled De | 被引量 : 0次 | 上传用户:meiaihui
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  Safe and efficient nucleic acid delivery remains a challenging task since several barriers have to be overcome within the delivery pathway,e.g.efficient nucleic acid complexation,prevention of unspeeific interaction,specific uptake into target cells and intracellular delivery to the site of action.Solid-phase synthesis can be used for the assembly of precise tailor-made poly(aminoamide)s and the site-specific integration of different modules [1,2].By this means a set of sequence-defined nucleic acid carriers containing a shielding polyethylene glycol (PEG),a peptidic ligand cMBP2 targeting the hepatocyte growth factor receptor (HGFR/c-Met),cysteines for bioreducible crosslinks and histidine residues for an increased endosomal buffer capacity was assembled.Alanines served as a negative control for the presence of a targeting ligand or histidines in the polymeric backbone.Important characteristics of the carriers,such as nucleic acid complexation potency,shielding,endosomal buffering and mediation of transgene expression were investigated.
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