Journal article
"Evolving nanoparticle gene delivery vectors for the liver: What has been learned in 30 years"
Journal of controlled release, Vol.219, pp.457-470
12/10/2015
DOI: 10.1016/j.jconrel.2015.10.008
PMID: 26439664
Abstract
Nonviral gene delivery to the liver has been under evolution for nearly 30years. Early demonstrations established relatively simple nonviral vectors could mediate gene expression in HepG2 cells which understandably led to speculation that these same vectors would be immediately successful at transfecting primary hepatocytes in vivo. However, it was soon recognized that the properties of a nonviral vector resulting in efficient transfection in vitro were uncorrelated with those needed to achieve efficient nonviral transfection in vivo. The discovery of major barriers to liver gene transfer has set the field on a course to design biocompatible vectors that demonstrate increased DNA stability in the circulation with correlating expression in liver. The improved understanding of what limits nonviral vector gene transfer efficiency in vivo has resulted in more sophisticated, low molecular weight vectors that allow systematic optimization of nanoparticle size, charge and ligand presentation. While the field has evolved DNA nanoparticles that are stable in the circulation, target hepatocytes, and deliver DNA to the cytosol, breaching the nucleus remains the last major barrier to a fully successful nonviral gene transfer system for the liver. The lessons learned along the way are fundamentally important to the design of all systemically delivered nanoparticle nonviral gene delivery systems.
Details
- Title: Subtitle
- "Evolving nanoparticle gene delivery vectors for the liver: What has been learned in 30 years"
- Creators
- Samuel T Crowley - Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA 52242,USAKevin G Rice - Division of Medicinal and Natural Products Chemistry, College of Pharmacy, University of Iowa, Iowa City, IA 52242,USA. Electronic address: kevin-rice@uiowa.edu
- Resource Type
- Journal article
- Publication Details
- Journal of controlled release, Vol.219, pp.457-470
- DOI
- 10.1016/j.jconrel.2015.10.008
- PMID
- 26439664
- NLM abbreviation
- J Control Release
- ISSN
- 0168-3659
- eISSN
- 1873-4995
- Publisher
- Netherlands
- Grant note
- GM097093 / NIGMS NIH HHS T32 GM008365 / NIGMS NIH HHS
- Language
- English
- Date published
- 12/10/2015
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Craniofacial Anomalies Research Center; Medicinal and Natural Products Chemistry
- Record Identifier
- 9984065324602771
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