"programmed packaging" for gene delivery

M. Hyodo, Y. Sakurai, H. Akita, H. Harashima

Research output: Contribution to journalArticlepeer-review

17 Citations (Scopus)

Abstract

We report on the development of a multifunctional envelope-type nano device (MEND) based on our packaging concept "Programmed packaging" to control not only intracellular trafficking but also the biodistribution of encapsulated compounds such as nucleic acids/proteins/peptides. Our strategy for achieving this is based on molecular mechanisms of cell biology such as endocytosis, vesicular trafficking, etc. In this review, we summarize the concept of programmed packaging and discuss some of our recent successful examples of using MENDs. Systematic evolution of ligands by exponential enrichment (SELEX) was applied as a new methodology for identifying a new ligand toward cell or mitochondria. The delivery of siRNA to tumors and the tumor vasculature was achieved using pH sensitive lipid (YSK05), which was newly designed and optimized under in vivo conditions. The efficient delivery of pDNA to immune cells such as dendritic cells has also been developed using the KALA ligand, which can be a breakthrough technology for DNA vaccine. Finally, ss-cleavable and pH-activated lipid-like surfactant (ssPalm) which is a lipid like material with pH-activatable and SS-cleavable properties is also introduced as a proof of our concept.

Original languageEnglish
Pages (from-to)316-323
Number of pages8
JournalJournal of Controlled Release
Volume193
DOIs
Publication statusPublished - 2014 Nov 10
Externally publishedYes

Keywords

  • Active targeting
  • Drug delivery system
  • Gene therapy
  • MEND
  • pDNA
  • siRNA

ASJC Scopus subject areas

  • Pharmaceutical Science

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