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Protein engineering approaches for regulating blood-brain barrier transcytosis.
Goulatis, Loukas I; Shusta, Eric V.
Afiliación
  • Goulatis LI; University of Wisconsin-Madison, Department of Chemical and Biological Engineering, 1415 Engineering Dr., Madison, WI 53706, United States of America.
  • Shusta EV; University of Wisconsin-Madison, Department of Chemical and Biological Engineering, 1415 Engineering Dr., Madison, WI 53706, United States of America. Electronic address: shusta@engr.wisc.edu.
Curr Opin Struct Biol ; 45: 109-115, 2017 08.
Article en En | MEDLINE | ID: mdl-28040636
The blood brain barrier (BBB) presents a challenge for the delivery of brain therapeutics. Trans-BBB delivery methods that use targeting vectors to coopt the vesicle trafficking machinery of BBB endothelial cells have been developed, but these are often hampered by limited flux through the BBB. A solution to this problem lies in the semi-rational engineering of BBB targeting vectors. Leveraging knowledge of intracellular trafficking, researchers have begun to tune selected binding properties of the vector-receptor interaction. Engineered binding affinity, avidity and pH-sensitivity have been shown to affect binding, intracellular sorting and release, ultimately leading to increased brain uptake of the targeting vector and its associated cargo. However, each targeted receptor may exhibit differential responses to engineered binding properties, illustrating the need to better understand vector-receptor interactions and trafficking dynamics.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Barrera Hematoencefálica / Ingeniería de Proteínas / Transcitosis Límite: Animals / Humans Idioma: En Revista: Curr Opin Struct Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Barrera Hematoencefálica / Ingeniería de Proteínas / Transcitosis Límite: Animals / Humans Idioma: En Revista: Curr Opin Struct Biol Asunto de la revista: BIOLOGIA MOLECULAR Año: 2017 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido