ABSTRACT
Although various earlier observations had shown that large polymers of lysine could
be used to deliver molecules into cells, the watershed moment for cell penetrating
peptides (CPPs)/protein-peptide transduction domains (PTDs) came in 1988 when
independent observations by Green and Loewenstein,1 and Frankel and Pabo2
showed that HIV1 TAT protein could enter cells. Although it took over 10 years to
go from a few papers published each year to well over a 100 papers each year, these
observations opened the door for formalizing macromolecular delivery. Conse-
quently, today we have many PTDs, many different types of cargo being delivered,
and many different ideas on the delivery mechanism across the cell membrane.
Although we are blessed in the richness and depth of our data, we have many
unanswered questions and have clearly not yet realized the full potential of
macromolecular delivery for clinically relevant therapeutics.
