Condensing peptide-DNA complexes have great potential as nonviral agents fo
r gene delivery. To date, however, such complexes have given transfection a
ctivities greatly inferior to adenovirus and somewhat inferior to cationic
lipid-DNA complexes, even for cell lines and primary cells in vitro. We rep
ort here the identification of a novel condensing peptide, CL22, which form
s DNA complexes that efficiently transfect many cell lines, as well as prim
ary dendritic and endothelial cells. We report studies with sequence and st
ructure variants that define some properties of the peptide that contribute
to efficient transfection. We demonstrate that the superior transfection a
ctivity of CL22 compared with other DNA condensing peptides is conferred at
a step after uptake of the complexes into cells. We show that CL22-DNA com
plexes have transfection activity that is at least equivalent to the best a
vailable nonviral agents.