Delivery of antisense peptide nucleic acids to cells by conjugation with small arginine-rich cell-penetrating peptide (R/W)9.

ABSTRACT: Peptide nucleic acids (PNAs) are very attractive antisense and antigene agents, but these molecules are not passively taken into cells. Here, using a functional cell assay and fluorescent-based methods, we investigated cell uptake and antisense activity of a tridecamer PNA that targets the HIV-1 polypurine tract sequence delivered using the arginine-rich (R/W)9 peptide (RRWWRRWRR). At micromolar concentrations, without use of any transfection agents, almost 80% inhibition of the target gene expression was obtained with the conjugate in the presence of the endosomolytic agent chloroquine. We show that chloroquine not only induced escape from endosomes but also enhanced the cellular uptake of the conjugate. Mechanistic studies revealed that (R/W)9-PNA conjugates were internalized via pinocyt

SUBMITTER: Cordier C 

PROVIDER: S-EPMC4134252 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature