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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 αν integrins. RGD-bearing mRNA complexes showed very high levels of expression, reaching over 60% transduction of B16F10 cells.

Original publication

DOI

10.1106/088391102027977

Type

Journal article

Journal

Journal of Bioactive and Compatible Polymers

Publication Date

01/01/2002

Volume

17

Pages

229 - 238