In vivo gene transfer using sulfhydryl cross-linked PEG-peptide/glycopeptide DNA co-condensates

Journal of Pharmaceutical Sciences
Kai Y KwokKevin G Rice

Abstract

Recent interest in sulfhydryl cross-linked nonviral gene delivery systems, designed to trigger the intracellular release of DNA, has inspired studies to establish their utility in vitro. To determine if this concept can be extrapolated to in vivo gene delivery, sulfhydryl cross-linking peptides (dp 20), derivatized with either an N-glycan or polyethylene glycol (PEG), were used to generate sulfhydryl cross-linked gene formulations. The biodistribution, metabolism, cell-type targeting, and gene expression of sulfhydryl cross-linked PEG-peptide/glycopeptide DNA co-condensates were examined following i.v. dosing in mice. Optimal targeting to hepatocytes was achieved by condensing (125)I-DNA with an add-mixture of 10 mol % triantennary glycopeptide, 5 mol % PEG-peptide, and 85 mol % backbone peptide. Four backbone peptides were substituted into the formulation to examine the influence of peptide metabolism and disulfide bond strength on the rate of DNA metabolism and the level of gene expression in vivo. The half-life of DNA in liver was extended from 1 to 3 h using a backbone peptide composed of d-amino acids, whereas substituting penicillamine for cysteine failed to further increase the metabolic stability of DNA. Optimized gene ...Continue Reading

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Citations

Jul 20, 2006·Bioconjugate Chemistry·Chang-Po ChenKevin G Rice
Mar 22, 2007·Bioconjugate Chemistry·Chang-po ChenKevin G Rice
Dec 9, 2009·Bioconjugate Chemistry·Nicholas J BaumhoverKevin G Rice
Feb 16, 2006·Proceedings of the National Academy of Sciences of the United States of America·Diana TrentinJeffrey A Hubbell
Apr 23, 2009·Expert Opinion on Drug Delivery·Chao Lin, Johan F J Engbersen
Jun 9, 2007·Expert Opinion on Biological Therapy·Garrett R Rettig, Kevin G Rice
Oct 20, 2006·Journal of Drug Targeting·Devika Soundara Manickam, David Oupický
Nov 22, 2005·Expert Opinion on Drug Delivery·David OupickyQing-Hui Zhou
Feb 10, 2009·Biomaterials·Fenghua MengZhiyuan Zhong
Oct 7, 2015·Journal of Controlled Release : Official Journal of the Controlled Release Society·Samuel T Crowley, Kevin G Rice
Dec 23, 2004·The Journal of Peptide Research : Official Journal of the American Peptide Society·C-P ChenK G Rice
Sep 19, 2006·Biomaterials·Thierry SchmitzAndreas Bernkop-Schnürch
Feb 21, 2006·Journal of Controlled Release : Official Journal of the Controlled Release Society·Takahito KawanoTakuro Niidome
Dec 11, 2003·Molecular Therapy : the Journal of the American Society of Gene Therapy·Assem-Galal ZiadyPamela B Davis
Oct 1, 2010·Advanced Materials·Sonja BauhuberAchim Göpferich
Dec 19, 2013·Journal of Postgraduate Medicine·N WadhwaA Tiwari
Mar 29, 2014·Macromolecular Bioscience·David Oupický, Jing Li
Nov 28, 2012·Advanced Healthcare Materials·Chaoliang HeXuesi Chen
Jul 28, 2016·Soft Matter·L PigeonP Midoux
Apr 24, 2009·Molecular Pharmaceutics·Christian A Fernandez, Kevin G Rice
Jan 5, 2008·Bioconjugate Chemistry·Markus RimannHeike Hall
Aug 16, 2006·Bioorganic & Medicinal Chemistry·Longhu ZhouPaul F Torrence
Oct 12, 2010·Molecular Pharmaceutics·Christopher R DrakeAndrew D Miller
Oct 22, 2011·Bioconjugate Chemistry·Véronique Bennevault-CeltonPatrick Midoux

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