Self-crosslinked and reducible fusogenic peptides for intracellular delivery of siRNA

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A novel self-crosslinked and reducible peptide was synthesized for stable formation of nanoscale complexes with an siRNA-PEG conjugate to enhance transfection efficiency in serum containing condition without compromising cytotoxicity. A fusogenic peptide, KALA, with two cystene residues at both terminal ends was crosslinked via disulfide linkages under mild DMSO oxidation condition. The reducible crosslinked KALA (cl-KALA) was used to form nano-complexes with green fluorescent protein (GFP) siRNA. Size and morphology of various polyelectrolyte complexes formulated with KALA and cl-KALA were comparatively analyzed. cl-KALA exhibited more reduced cell cytotoxicity and formed more stable and compact polyelectrolyte complexes with sIRNA, compared with naked KALA and polyethylenimine (PEI), probably because of its increased charge density. The extent of gene silencing was quantitatively evaluated using MDA-MB-435 cells. cl-KALA/siRNA complexes showed comparable gene silencing efficiency with those of cytotoxic PEI. In a serum containing medium, cl-KALA/siRNA-PEG conjugate complexes exhibited superior gene inhibition because of the shielding effect of PEG on the surface. The formulation based on the self-crosslinked fusogenic peptide could be used as a biocompatible and efficient nonviral carrier for siRNA delivery. (c) 2008 Wiley Periodicals, Inc.
Publisher
WILEY-BLACKWELL
Issue Date
2008-10
Language
English
Article Type
Article
Keywords

GENE DELIVERY; IN-VITRO; RNA INTERFERENCE; NUCLEIC-ACIDS; VEGF SIRNA; COMPLEXES; VIVO; DNA; POLYETHYLENIMINE; ACTIVATION

Citation

BIOPOLYMERS, v.89, no.10, pp.881 - 888

ISSN
0006-3525
DOI
10.1002/bip.21032
URI
http://hdl.handle.net/10203/10761
Appears in Collection
BS-Journal Papers(저널논문)
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