Conference proceeding
Efficient nuclear delivery and nuclear body localization of antisense oligo-nucleotides using degradable polymersomes
2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15, 5340
01 Jan 2006
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Efficient nuclear delivery and nuclear body localization of antisense oligo-nucleotides using degradable polymersomes
- Creators
- Younghoon Kim - Univ Penn, Penn Muscle Inst, Dept Chem & Biomol Engn, Philadelphia, PA 19104 USAManu Tewari - Univ Penn, Penn Muscle Inst, Dept Chem & Biomol Engn, Philadelphia, PA 19104 USADavid J. Pajeroski - Univ Penn, Penn Muscle Inst, Dept Chem & Biomol Engn, Philadelphia, PA 19104 USAShamik Sen - Univ Penn, Penn Muscle Inst, Dept Chem & Biomol Engn, Philadelphia, PA 19104 USAWilliams Jason - Drexel Univ, Coll Med, Dept Pharmacol, Philadelphia, PA USAShashank Sirsi - Drexel Univ, Coll Med, Dept Pharmacol, Philadelphia, PA USAGordon Lutz - Drexel UniversityDennis E. Discher - Univ Penn, Penn Muscle Inst, Dept Chem & Biomol Engn, Philadelphia, PA 19104 USAIEEE
- Publication Details
- 2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-15, 5340
- Conference
- 2006 28TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, 28th
- Publisher
- IEEE
- Number of pages
- 2
- Grant note
- NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA NTI MRSEC; National Science Foundation (NSF) NSF; National Science Foundation (NSF)
- Resource Type
- Conference proceeding
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Identifiers
- 991019170604904721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Engineering, Biomedical