Transcytosis in the blood–cerebrospinal fluid barrier of the mouse brain with an engineered receptor/ligand system

作者: Héctor R Méndez-Gómez , Albert Galera-Prat , Craig Meyers , Weijun Chen , Jasbir Singh

DOI: 10.1038/MTM.2015.37

关键词: Transferrin receptorTransferrinPathologyReceptorChoroid plexusDockerinLigand (biochemistry)Cell biologyCohesin domainMedicineTranscytosis

摘要: Crossing the blood–brain and blood–cerebrospinal fluid barriers (BCSFB) is one of fundamental challenges in development new therapeutic molecules for brain disorders because these prevent entry most drugs from blood into brain. However, some large molecules, like protein transferrin, cross using a specific receptor that transports them Based on this mechanism, we engineered receptor/ligand system to overcome by combining human transferrin with cohesin domain Clostridium thermocellum, tested hybrid choroid plexus mouse dockerin ligand. By expressing our choroidal ependymocytes, which are part BCSFB, found systemically administrated ligand was able bind accumulate where transported side side.

参考文章(41)
W A Jefferies, S V Hunt, A F Williams, M R Brandon, Analysis of lymphopoietic stem cells with a monoclonal antibody to the rat transferrin receptor. Immunology. ,vol. 54, pp. 333- 341 ,(1985)
Ningya Shi, Ruben J. Boado, William M. Pardridge, Receptor-mediated gene targeting to tissues in vivo following intravenous administration of pegylated immunoliposomes Pharmaceutical Research. ,vol. 18, pp. 1091- 1095 ,(2001) , 10.1023/A:1010910523202
Vivian W. Choi, Aravind Asokan, Rebecca A. Haberman, Richard Jude Samulski, Production of recombinant adeno-associated viral vectors for in vitro and in vivo use. Current protocols in molecular biology. ,vol. 78, ,(2007) , 10.1002/0471142727.MB1625S78
S Zolotukhin, M Potter, W W Hauswirth, J Guy, N Muzyczka, A "humanized" green fluorescent protein cDNA adapted for high-level expression in mammalian cells. Journal of Virology. ,vol. 70, pp. 4646- 4654 ,(1996) , 10.1128/JVI.70.7.4646-4654.1996
Torben Moos, Evan H. Morgan, Transferrin and Transferrin Receptor Function in Brain Barrier Systems Cellular and Molecular Neurobiology. ,vol. 20, pp. 77- 95 ,(2000) , 10.1023/A:1006948027674
Nadia Benaroudj, Alfred L. Goldberg, PAN, the proteasome-activating nucleotidase from archaebacteria, is a protein-unfolding molecular chaperone. Nature Cell Biology. ,vol. 2, pp. 833- 839 ,(2000) , 10.1038/35041081
Michal Slutzki, Yoav Barak, Dan Reshef, Ora Schueler-Furman, Raphael Lamed, Edward A. Bayer, Indirect ELISA-based approach for comparative measurement of high-affinity cohesin-dockerin interactions. Journal of Molecular Recognition. ,vol. 25, pp. 616- 622 ,(2012) , 10.1002/JMR.2178
V Wohlgensinger, R Seger, M D Ryan, J Reichenbach, U Siler, Signed outside: a surface marker system for transgenic cytoplasmic proteins Gene Therapy. ,vol. 17, pp. 1193- 1199 ,(2010) , 10.1038/GT.2010.73
Sifeng Chen, Matthias Kapturczak, Scott A. Loiler, Sergei Zolotukhin, Olena Y. Glushakova, Kirsten M. Madsen, Richard J. Samulski, William W. Hauswirth, Martha Campbell-Thompson, Kenneth I. Berns, Terence R. Flotte, Mark A. Atkinson, C. Craig Tisher, Anupam Agarwal, Efficient transduction of vascular endothelial cells with recombinant adeno-associated virus serotype 1 and 5 vectors. Human Gene Therapy. ,vol. 16, pp. 235- 247 ,(2005) , 10.1089/HUM.2005.16.235