Reducible poly(oligo-d-arginine) for enhanced gene expression in mouse lung by intratracheal injection

Young Wook Won, Hyun Ah Kim, Minhyung Lee, Yong Hee Kim

Research output: Contribution to journalArticlepeer-review

87 Scopus citations

Abstract

Nonarginine (D-R9) has been reported to be one of the most efficacious protein transduction domains (PTDs) for the intracellular cargo delivery such as DNA, RNA, proteins, and particles. Although oligoarginines are capable of forming polyplex with DNA by electrostatic interaction, the length of oligoarginine can affect the toxicity and gene expression. The reducible poly(oligo-D-arginine) (rPOA) composed of the Cys-(D-R9)-Cys repeating unit forming disulfide bonds between terminal cysteinyl-thiol groups of short peptides was hypothesized to show efficient gene transfection without toxicity. The reducible high molecular weight poly(oligo-D-arginine) may fragment into the Cys-(D-R9)-Cys in cellular environments such as cytosol, cell surface, endosomes, and lysosomes, and enhance DNA transfection efficiency. In the present study, in vitro stability, cytotoxicity, and transfection efficiency of DNA/poly(oligo-D-arginine) polyplex were evaluated. In addition, in vivo delivery of DNA into the lung was performed by intratracheal injection of DNA/poly(oligo-D-arginine) polyplex. The in vivo study with rPOA showed higher level of gene expression than PEI, sustaining for 1 week without toxicity. Reducible high molecular weight poly(oligo-D-arginine) based on R9 PTD is a very promising nonviral gene carrier for lung diseases by efficiently condensing, stabilizing, and transfecting DNA.

Original languageEnglish (US)
Pages (from-to)734-742
Number of pages9
JournalMolecular Therapy
Volume18
Issue number4
DOIs
StatePublished - Apr 2010
Externally publishedYes

ASJC Scopus subject areas

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

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