Efficient nuclear delivery and nuclear body localization of antisense oligo-nucleotides using degradable polymersomes

Kim Younghoon, Manu Tewari, David J. Pajeroski, Shamik Sen, Williams Jason, Shashank Sirsi, Gordon Lutz, Dennis E. Discher

Research output: Chapter in Book/Report/Conference proceedingConference contribution

Abstract

Delivery of antisense oligonucleotides, AON, presents many of the same challenges as delivery of any nucleic acid: charge, stability, cell uptake, endolysosomal escape, and entry into the nucleus. Here we demonstrate efficient delivery of AON after loading into biodegradable polymer vesicles or 'polymersomes'. We focus on AON delivery to muscle cells in vitro and in vivo because of the emergence of AON in therapeutic strategies directed at muscular dystrophies. To first clarify uptake kinetics without the complications of typical multi-layered myotube cultures, we use micro-patterned C2C12 cells and show efficient uptake of AON-polymersomes. The biodegradable polymersomes break down and foster AON escape with the binding of fluorescent-AON into the nuclear bodies. Intramuscular injections of the polymersome-AON into the hind limbs of mdx-dystrophic mice show more efficient nuclear uptake than AON alone and also lead to dystrophin expression in the mdx mice. In sum, these neutral, degradable carriers of AON show promise in vivo.

Original languageEnglish (US)
Title of host publication28th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS'06
Pages4350-4353
Number of pages4
DOIs
StatePublished - Dec 1 2006
Event28th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS'06 - New York, NY, United States
Duration: Aug 30 2006Sep 3 2006

Other

Other28th Annual International Conference of the IEEE Engineering in Medicine and Biology Society, EMBS'06
CountryUnited States
CityNew York, NY
Period8/30/069/3/06

ASJC Scopus subject areas

  • Signal Processing
  • Biomedical Engineering
  • Computer Vision and Pattern Recognition
  • Health Informatics

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