Please cite as: CSH Protocols; 2006; doi:10.1101/pdb.prot4450

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Bioresponsive Targeted Charge Neutral Lipid Vesicles for Systemic Gene Delivery

Weijun Li and Francis C. Szoka, Jr.1

Department of Biopharmaceutical Sciences and Pharmaceutical Chemistry, School of Pharmacy, University of California at San Francisco, California 94143-0446, USA

1Corresponding author (szoka{at}cgl.ucsf.edu)


INTRODUCTION

This protocol describes a stepwise procedure to prepare nucleic acids encapsulated in a polyethylene glycol (PEG)-shielded nanolipoparticle (NLP) that contain a bioresponsive lipid and ligand. This process provides several advantages for systemic gene delivery. The in vivo circulation time is extended. Also, low pH-sensitive lipids enhance DNA unpacking and endosomal escape. Finally, ligands inserted into the NLP surface can target gene delivery to specific tissues or cells in vivo.


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