Cell-penetrating peptides, such as the HIV TAT peptide, are able to enter cells using a number of mechanisms, from direct entry to endocytosis, a process by which cells internalize molecules by engulfing them.
Further, these cell-penetrating peptides, or CPPs, can facilitate the cellular transfer of various molecular cargoes, from small chemical molecules to nano-sized particles and large fragments of DNA. Because of this ability, CPPs hold great potential as in vitro and in vivo delivery vehicles for use in research and for the targeted delivery of therapeutics to individual cells.
But exactly how cell-penetrating peptides and particularly the HIV TAT peptide accomplish these tasks has so far been a mystery.
"The HIV TAT peptide is special. People discovered that one can attach almost anything to this peptide and it could drag it across the cell," said Gerard Wong, a professor of bioengineering and of chemistry and biochemistry at the UCLA Henry Samueli School of Engineering and Applied Science and the California NanoSystems Institute at UCLA. "So there are obvious beneficial drug-delivery and biotechnology applications."
In a new study published in Proceedings of the National Academy of Sciences, UCLA Engineering researchers, including Wong and bioengineering professors Timothy Deming and Daniel Kamei, identify how HIV TAT peptides can have multiple interactions with the cell membrane, the actin cytoskeleton and specific cell-surface receptors to produce multiple pathways of translocation under different conditions.
Moreover, because the researchers now understand how cell-penetrating peptides work, they say it is possible to formulate a general recipe for reprograming normal peptides into CPPs.
"Prior to this, people didn't really know how it all worked, but we found that the HIV TAT peptide is really kind of like a Swiss Army Knife molecule, in that it can interact very strongly with membr
|Contact: Wileen Wong Kromhout|
University of California - Los Angeles