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Development of a Nonviral Gene Delivery Vehicle for Systemic Application

Pun, Suzie Hwang and Davis, Mark E. (2002) Development of a Nonviral Gene Delivery Vehicle for Systemic Application. Bioconjugate Chemistry, 13 (3). pp. 630-639. ISSN 1043-1802. doi:10.1021/bc0155768.

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Polycation vehicles used for in vitro gene delivery require alteration for successful application in vivo. Modification of polycations by direct grafting of additional components, e.g., poly(ethylene glycol) (PEG), either before or after DNA complexation, tend to interfere with polymer/DNA binding interactions; this is a particular problem for short polycations such as linear, β-cyclodextrin-containing polycations (βCDPs). Here, a new method of βCDP polyplex (polycation/DNA composite structures) modification is presented that exploits the ability to form inclusion complexes between cyclodextrins and adamantane. Surface-PEGylated βCDP polyplexes are formed by self-assembly of the polyplexes with adamantane−PEG conjugates. While unmodified polyplexes rapidly aggregate and precipitate in salt solutions, the PEGylated βCDP polyplexes are stable at conditions of physiological salt concentration. Addition of targeting ligands to the adamantane−PEG conjugates allows for receptor-mediated delivery; galactosylated βCDP-based particles reveal selective targeting to hepatocytes via the asialoglycoprotein receptor. Galactosylated particles transfect hepatoma cells with 10-fold higher efficiency than glucosylated particles (control), but show no preferential transfection in a cell line lacking the asialoglycoprotein receptor. Thus, surface modification of βCDP-based polyplexes through the use of cyclodextrin/adamantane host/guest interactions endows the particles with properties appropriate for systemic application.

Item Type:Article
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URLURL TypeDescription
Pun, Suzie Hwang0000-0003-1443-4996
Davis, Mark E.0000-0001-8294-1477
Additional Information:© 2002 American Chemical Society. Received 2 November 2001; Published online 20 April 2002; Published in print 1 May 2002. S.J.H. thanks the Whitaker Foundation for financial support for the portion of research conducted at the California Institute of Technology. S.J.H. is also grateful for helpful discussions with Dr. Nathalie Bellocq (Insert Therapeutics) and Prof. John Brady (Caltech). M.E.D. is a consultant to and has financial interest in Insert Therapeutics.
Funding AgencyGrant Number
Whitaker FoundationUNSPECIFIED
Issue or Number:3
Record Number:CaltechAUTHORS:20170125-093852983
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Official Citation:Development of a Nonviral Gene Delivery Vehicle for Systemic Application Suzie Hwang Pun†,‡ and and Mark E. Davis*,† Bioconjugate Chemistry 2002 13 (3), 630-639 DOI: 10.1021/bc0155768
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:73710
Deposited By: Ruth Sustaita
Deposited On:25 Jan 2017 18:57
Last Modified:11 Nov 2021 05:20

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