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US 10,246,504 B2Granted
Engineered receptor and their use
AssigneeUniversity of Pittsburgh—Of the Commonwealth System of Higher Education
InventorsYan Xu, Pei Tang, Tommy S. Tillman
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Abstract
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.
Claims19
A chloride channel receptor, comprising:
- a) a transmembrane domain of a mammalian glycine receptor in the absence of the extracellular and intracellular domains of the mammalian glycine receptor, wherein the transmembrane domain comprises domains transmembrane (TM) 1, TM2, and TM3, wherein the transmembrane domain comprises a mutation at S16′ of the TM2;
- and
- b) an extracellular domain of a pH-gated pentameric ligand-gated ion channel from Gloeobacter violaceus (GLIC);
- and
- 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 the interfacial sequences and C-terminus are from Gloeobacter violaceus or a human;
- and wherein opening of the chloride channel receptor is induced by pH.
3 more elements
Dependencies are inferred from the claim text.