Transport molecules using reverse sequence HIV-Tat polypeptides: not just any old Tat? (WO200808225).
BACKGROUND
Many polycationic cell penetrating peptides (CPPs), alternatively named protein transduction domains, have been used for the efficient intracellular delivery of biologically active agents. Patent WO2008/082885 relates to the properties and proposed biomedical applications of a CPP and putative-related sequences that represent the reverse sequence of a nonapeptide basic domain of the HIV-transactivator protein (Tat) (RRRQRRKKR).


OBJECTIVE
This evaluation critically assesses the reported utility of such transport molecules and the numerous potential embodiments of the invention, in comparison with other recent developments in the field. We also review recent biomedical applications of Tat-derived peptide transporters.


METHODS
The scope of this review includes both Tat-derived peptide transporters and other sequence-related CPPs that are polycationic in nature.


CONCLUSIONS
The patent application indicates that reverse sequence HIV-Tat polypeptides can increase the transdermal delivery of an iodinated mixture of botulinum toxin, albumin and accessory proteins (Neuronox), Medy-Tox, Inc., Seoul, South Korea) as a non-covalent complex. Moreover, the invention also contemplates all variants of the reverse-sequence polypeptide and claims a variety of potential biomedical applications using the reverse sequence peptide as a delivery vector. Unfortunately, in the absence of both rigorous comparative data and toxicological analyses, it is uncertain if these transport molecules offer any advantages compared with many existing and rigorously characterised CPP vector systems.
Howl
John
J
University of Wolverhampton, Research Institute in Healthcare Science, School of Applied Sciences, Wulfruna Street, Wolverhampton, WV1 1LY, UK. Howl@wlv.ac.uk
Jones
Sarah
S
D000595:Amino Acid Sequence; D000818:Animals; D019274:Botulinum Toxins, Type A / Q000008:administration & dosage / Q000493:pharmacokinetics; D002412:Cations; D002462:Cell Membrane / Q000378:metabolism; D016503:Drug Delivery Systems; D006801:Humans; D010330:Patents as Topic; D010455:Peptides / Q000378:metabolism*; D021381:Protein Transport; D012869:Skin Absorption; D054322:tat Gene Products, Human Immunodeficiency Virus / Q000378:metabolism*
D002412:Cations; D010455:Peptides; D054322:tat Gene Products, Human Immunodeficiency Virus; D019274:Botulinum Toxins, Type A