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Journal of Bioactive and Compatible Polymers
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Targeting of Polyelectrolyte RNA Complexes to Cell Surface Integrins as an Efficient Cytoplasmic Transfection Mechanism

Alan L. Parker

Cancer Research UK Institute for Cancer Studies, University of Birmingham, Birmingham B15 2TA United Kingdom

Leonard W. Seymour

Department of Clinical Pharmacology, University of Oxford, Radcliffe Infirmary, Woodstock Road, Oxford OX2 6HE.Len.Seymour{at}clinpharm.ox.ac.uk

This is the first demonstration of receptor-mediated delivery of mRNA and establishes a new approach to gene therapy. Messenger RNA (mRNA) provides a promising alternative to plasmid DNA as a genetic material for delivery in non-viral gene therapy strategies. Since it does not require access to the nucleus and is less dependent on the cell cycle for expression, mRNA delivered using cationic lipids or short cationic polymers can be effectively translated within target cells. In this study, mRNA formed discrete nanoparticles following self assembly with a range of cationic polymers. Based on transfection activities, the low molecular weight polycations were more efficient than high molecular weight, while protamine and polyethylenimine were far more efficient than poly(L-lysine). Receptor-mediated delivery of mRNA was demonstrated using the synthetic polyamino acid (K)16GACDCRGDCFCA designed to promote cell entry following interaction with cell surface {alpha}{upsilon} integrins. RGD-bearing mRNA complexes showed very high levels of expression, reaching over 60% transduction of B16F10 cells.

Key Words: RNA • transfection • RGD • integrin • gene therapy • gene delivery

Journal of Bioactive and Compatible Polymers, Vol. 17, No. 4, 229-238 (2002)
DOI: 10.1106/088391102027977
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