摘要 |
Engineered chloride channel receptors, nucleic acids encoding these receptors, expression vectors including these nucleic acids are disclosed herein. Nanoparticles and pharmaceutical compositions including these engineered chloride channel receptors, nucleic acids, and expression vectors are disclosed. The use of these compositions and nanoparticles, such as for the treatment of pain, cystic fibrosis and asthma, is also disclosed. |
主权项 |
1. A chloride channel receptor, comprising:
a) a transmembrane domain of a glycine receptor in the absence of the extracellular and intracellular domains of the glycine receptor, wherein the transmembrane domain comprises domains TM1, TM2, TM3; and b) an extracellular domain of a pH-gated pentameric ligand-gated ion channel from Gloeobacter violaceus (GLIC) or an extracellular domain of an amine-activated pLGIC from Erwinia chrysanthemi (ELIC); c) interfacial sequences between the extracellular domain and transmembrane domain*, wherein the interfacial sequences comprise, in N-terminal to C-terminal order, loop 2, loop 7, loop 9, pre-TM1 linker, TM2-TM3 linker, and C-terminus, wherein loop 2, loop 7 loop 9, pre-TM 1 linker, TM2-TM3 linker, and C-terminus are from Gloeobacter violaceus, Erwinia chrysanthemi or a human; and wherein opening of the chloride channel receptor is induced by pH or by an activating molecule. |