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

Nathan P. Gabrielson, Hua Lu, Lichen Yin, Kyung Hoon Kim, Jianjun Cheng

Research output: Contribution to journalArticle

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 polypeptidePVBLGn-8that is able to adopt a helical structure independent of pH. Like other CPPs, the helical structure of PVBLGn-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 PVBLGn-8 are irreversible. Given its pH-insensitive activity, our results suggest that PVBLGn-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.

Original languageEnglish (US)
Pages (from-to)1599-1609
Number of pages11
JournalMolecular Therapy
Volume20
Issue number8
DOIs
StatePublished - Aug 2012

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Small Interfering RNA
Cell-Penetrating Peptides
Polymers
Membranes
Endosomes
Cytosol
Cell Membrane
Peptides
Pharmaceutical Preparations
Genes

ASJC Scopus subject areas

  • Molecular Medicine
  • Molecular Biology
  • Genetics
  • Pharmacology
  • Drug Discovery

Cite this

A cell-penetrating helical polymer for siRNA delivery to mammalian cells. / Gabrielson, Nathan P.; Lu, Hua; Yin, Lichen; Kim, Kyung Hoon; Cheng, Jianjun.

In: Molecular Therapy, Vol. 20, No. 8, 08.2012, p. 1599-1609.

Research output: Contribution to journalArticle

Gabrielson, Nathan P. ; Lu, Hua ; Yin, Lichen ; Kim, Kyung Hoon ; Cheng, Jianjun. / A cell-penetrating helical polymer for siRNA delivery to mammalian cells. In: Molecular Therapy. 2012 ; Vol. 20, No. 8. pp. 1599-1609.
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