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A cell-penetrating helical polymer for siRNA delivery to mammalian cells.

ABSTRACT: Cell-penetrating peptides (CPPs) are routinely used for intracellular delivery of a variety of cargo, including drugs, genes, and short interfering RNA (siRNA). Most CPPs are active only upon exposure to acidic environments inside of late endosomes, thereby facilitating the endosomal escape of internalized vectors. Here, we describe the generation of a synthetic polypeptide--PVBLG(n)-8--that is able to adopt a helical structure independent of pH. Like other CPPs, the helical structure of PVBLG(n)-8 allows the polypeptide to destabilize membranes. However, since the helix is stable at all physiologically relevant pH values between pH 2 and pH 7.4, the membrane permeation properties of PVBLG(n)-8 are irreversible. Given its pH-insensitive activity, our results suggest that PVBLG(n)-8 is able to facilitate efficient siRNA delivery by causing pore formation in the cell membranes through which either free or complexed siRNA is able to diffuse. This nonspecific form of entry into the cell cytosol may prove useful when trying to deliver siRNA to cells which have proven to be difficult to transfect.

SUBMITTER: Gabrielson NP 

PROVIDER: S-EPMC3412491 | BioStudies | 2012-01-01T00:00:00Z

REPOSITORIES: biostudies

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