Cellular siRNA delivery using cell-penetrating peptides modified for endosomal escape

Tamaki Endoh, Takashi Ohtsuki

Research output: Contribution to journalReview articlepeer-review

219 Citations (Scopus)


RNAi-mediated silencing of specific genes is a promising strategy for gene therapy. To utilize RNAi for therapy, an efficient and safe method for delivery of RNA into the cell cytosol is necessary. The plasma membrane is the primary, and most difficult, barrier for RNA to cross, because negatively charged RNA is strongly repulsed by the negatively charged membrane. A variety of cationic polymers can be used as RNA carriers by interacting with RNA and covering its negative charges to form a cell-penetrating complex. Among the emerging candidates for RNA carriers are cationic cell-penetrating peptides (CPPs), which can cross the plasma membrane and internalize into cells together with RNA. This review focuses on CPP-based RNA delivery strategies. In using CPP-based RNA delivery, most of the RNA internalized by the cell is entrapped in endosomes. Strategies for endosomal escape of RNAs are also reviewed.

Original languageEnglish
Pages (from-to)704-709
Number of pages6
JournalAdvanced Drug Delivery Reviews
Issue number9
Publication statusPublished - Jul 25 2009


  • Cell-penetrating peptide
  • Photoinduced endosomal escape
  • RNAi
  • shRNA
  • siRNA

ASJC Scopus subject areas

  • Pharmaceutical Science


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