Peptide-enhanced cationic lipid transfections

DETAILED DESCRIPTION OF THE INVENTION The present invention provides improved methods for transfecting eukaryotic cells with nucleic acids by employing peptides or modified peptides in combination with transfection agents, e.
g.
, cationic lipids and dendrimers.
The improvement relates in one aspect to the use of a peptide-nucleic acid complex to enhance the efficiency of cationic lipid-mediated or dendrimer-mediated transfection.
The peptide-nucleic acid complex comprises peptide bound to nucleic acid or a peptide modified to be covalently conjugated to a nucleic acid-binding group which is then bound to nucleic acid.
This invention has significant advantages over prior art methods of transfection which employ cationic lipids or dendrimers for transfection.
The peptides of this invention include fusagenic peptides, membrane-permeabilizing peptides, nuclear localization peptides, and receptor-ligand peptides, among others.
Receptor-ligand peptides include among others cell-adhesion peptides, cell-targeting peptides, internalization-triggering peptides, and endocytosis-triggering peptides.
Peptides useful in this invention can include peptide sequences functional for fusion (fusagenic sequences), sub-cellular localization or which mediate binding to a receptor.
A peptide may be multi-functional comprising sequences with more than one of these functions.
Peptides are optionally covalently coupled to a nucleic-binding group including a polyamine and form a complex with the nucleic acid.
Peptide-complexed nucleic acids are more efficiently transported into the cells and the cell nucleus, thus enhancing the efficiency of cationic lipid- or dendrimer-mediated cell transfection.
Because of the improved efficiency of transfection, considerably less nucleic acid is required for effective transfection.
Transfection compositions of this invention, by virtue of complex formation between the nucleic acid and peptide or modified peptide, provide enhanced transfection as compared to prior art cationic lipid and dendrimer transfection compositions