Individuals unlucky enough to be born with a genetic defect that results in them having no purine nucleoside phosphorylase (PNP), an enzyme that helps get rid of unwanted material in the cell, usually die early in life from infections, autoimmunity, and cancer. There is currently no treatment for most individuals lacking PNP, in part because it is necessary to replace PNP inside their cells, a very difficult task. Now, in a study appearing online on September 7 in advance of publication in the October print issue of the Journal of Clinical Investigation, researchers from the University of Toronto have found a way to get PNP into the cells of Pnp-deficient mice.
Some proteins can enter cells because they have a domain known as a protein transduction domain (PTD). So, Eyal Grunebaum and Ana Toro attached the PTD of another protein to PNP and showed that this PTD-PNP fusion protein could enter cells when it was administered to Pnp-deficient mice. Furthermore, frequent administration of the PTD-PNP fusion protein to Pnp-deficient mice corrected most of their defects, including their immune defects. This study might be the first step to developing a treatment for individuals lacking PNP. If this technology were to prove successful it could also be applied to other diseases caused by defects in proteins inside cells.
TITLE: TAT-mediated intracellular delivery of purine nucleoside phosphorylase corrects its deficiency in mice
AUTHOR CONTACT:
Eyal Grunebaum
Hospital for Sick Children and University of Toronto, Toronto, Ontario, Canada.
Phone : 416-813-8623; Fax: 416-813-8624; E-mail: eyal.grunebaum@sickkids.ca
View the PDF of this article at: https://www.the-jci.org/article.php?id=25052
Journal of Clinical Investigation