Sonogenic stimulation of cells

Abstract

The invention provides compositions featuring TRP-4 polypeptides and polynucleotides, methods for expressing such polypeptides and polynucleotides in a cell type of interest, and methods for inducing the activation of the TRP-4 polypeptide in neurons and other cell types using ultrasound.

1 . An imaging and ultrasound exposure system for altering the function of nerve cells that innervate a targeted tissue portion of a mammalian subject, the system comprising an imaging source and an ultrasound source comprising a ultrasound beam focusing transducer; wherein said ultrasound source of the system (i) delivers ultrasound to an exposed surface of the mammalian subject; (ii) provides ultrasound energy to the innervated targeted tissue portion, wherein the nerve cells that innervate the targeted tissue portion are configured to express an ultrasound-sensitive, exogenous TRP-N or TRP-4 transmembrane protein; and (iii) modulates the membrane potential of the nerve cells comprising the targeted tissue structure when the targeted tissue portion of the animal is exposed to ultrasound energy from the ultrasound source. 
     
     
         2 . The system of  claim 1 , wherein the nerve cells are genetically modified to express the exogenous TRP-N transmembrane protein. 
     
     
         3 . The system of  claim 1 , wherein the nerve cells are genetically modified to express the exogenous TRP-4 transmembrane protein. 
     
     
         4 . The system of  claim 2 , wherein the exogenous TRP-N transmembrane protein is a non-mammalian TRP-N transmembrane protein. 
     
     
         5 . The system of  claim 3 , wherein the exogenous TRP-4 transmembrane protein is a non-mammalian TRP-4 transmembrane protein. 
     
     
         6 . The system of  claim 1 , wherein said TRP-4 polypeptide is encoded by a polynucleotide codon-optimized for expression in the cell. 
     
     
         7 . The system of  claim 1 , wherein the exogenous TRP-4 polypeptide comprises an amino acid sequence having at least 85% identity to the amino acid sequence of SEQ ID NO: 1. 
     
     
         8 . The system of  claim 1 , wherein the exogenous TRP-4 polypeptide comprises the amino acid sequence of SEQ ID NO: 1. 
     
     
         9 . The system of  claim 1 , wherein the ultrasound source comprises an ultrasound transducer. 
     
     
         10 . The system of  claim 1 , wherein the nerve cells are motor neurons, sensory neurons, or interneurons. 
     
     
         11 . The system of  claim 1 , wherein the mammalian subject is a human subject. 
     
     
         12 . The system of  claim 1 , wherein the nerve cells are transduced using a vector comprising a polynucleotide sequence encoding the exogenous TRP-N polypeptide or using a recombinant nucleic acid molecule encoding the exogenous TRP-N polypeptide. 
     
     
         13 . The system of  claim 1 , wherein the nerve cells are transduced using a vector comprising a polynucleotide sequence encoding the exogenous TRP-4 polypeptide or using a recombinant nucleic acid molecule encoding the exogenous TRP-4 polypeptide. 
     
     
         14 . The system of  claim 1 , wherein the ultrasound has a frequency of about 0.8 MHz to about 4 MHz. 
     
     
         15 . The system of  claim 1 , wherein said ultrasound has a focal zone of about 1 cubic millimeter to about 1 cubic centimeter. 
     
     
         16 . The system of  claim 1 , wherein the system operates with an ultrasound frequency of at least 20 kHz.