首页 | 本学科首页   官方微博 | 高级检索  
   检索      


HIV-1 TAT-mediated protein transduction of human HPRT into deficient cells
Authors:Paola Cattelan  Diego DolcettaUros Hladnik  Elisabetta Fortunati
Institution:‘Mauro Baschirotto’ Institute for Rare Diseases–B.I.R.D., 36023 Costozza di Longare, Vicenza, Italy
Abstract:Lesch–Nyhan disease (LND) is a severe and incurable X-linked genetic syndrome caused by the deficiency of hypoxanthine–guanine phosphoribosyltransferase (HPRT), resulting in severe alterations of central nervous system, hyperuricemia and subsequent impaired renal functions. Therapeutic options consist in supportive care and treatments of complications, but the disease remains largely untreatable. Enzyme replacement of the malfunctioning cytosolic protein might represent a possible therapeutic approach for the LND treatment. Protein transduction domains, such as the TAT peptide derived from HIV TAT protein, have been used to transduce macromolecules into cells in vitro and in vivo. The present study was aimed to the generation of TAT peptide fused to human HPRT for cell transduction in enzyme deficient cells. Here we document the construction, expression and delivery of a functional HPRT enzyme into deficient cells by TAT transduction domain and by liposome mediated protein transfer. With this approach we demonstrate the correction of the enzymatic defect in HPRT deficient cells.
Keywords:Lesch&ndash  Nyhan disease  HPRT  Recombinant proteins  Protein purification  TAT transduction domain  Enzyme replacement therapy
本文献已被 ScienceDirect 等数据库收录!
设为首页 | 免责声明 | 关于勤云 | 加入收藏

Copyright©北京勤云科技发展有限公司  京ICP备09084417号