Biologic device for regulation of gene expression and method therefor

Abstract

A system and device are provided which include a gene regulatory system controlling expression of one or more expression cassettes present in or released by the device, by emitting one or more stimulations. An expression cassette includes a regulatable transcription control element that is responsive to the emitted stimulations linked to an open reading frame of interest. The system optionally includes a sensor to sense a parameter indicative of a need, a telemetry module to receive an external command, or a programmable device, for regulating gene expression of the open reading frame.

1 . A system comprising: 
 a lead including a lead body extending from a proximal end portion to a distal end portion;    one or more gene depositories disposed along the lead body, the one or more gene depositories include a porous, biocompatible and substantially nonbiodegradable material, wherein the material is selected to allow the passage of soluble cellular factors and prevent passage of cells across the material; and    one or more gene regulatory stimulators associated with the one or more gene depositories, the one or more gene regulatory stimulators emit a regulatory stimulation capable of regulating a regulatable transcription control element in an expression cassette including the regulatable transcription control element operably linked to an open reading frame of interest or in an endogenous gene which includes the regulatable transcription control element operably linked to an open reading frame of interest.    
     
     
         2 . The system of  claim 1 , further comprising a physiological parameter sensor, the sensor adapted to sense a physiological parameter indicative of a predetermined cardiac condition.  
     
     
         3 . The system of  claim 2 , further comprising 
 a controller coupled to the sensor and one or more of the gene regulatory stimulators, the controller adapted to control the emission of the regulatory stimulation based on at least the sensed physiological parameter.    
     
     
         4 . The system of  claim 1 , further comprising 
 a controller coupled to a telemetry module, the telemetry module adapted to receive an external command, and the controller adapted to control emission of the regulatory stimulation based on at least the external command.    
     
     
         5 . The system of  claim 1 , further comprising 
 a controller associated with a programmable device, the controller adapted to control emission of the regulatory stimulation based on a predetermined program executed by the programmable device.    
     
     
         6 . The system of  claim 1 , wherein the one or more gene depositories comprise recombinant virus comprising the expression cassette.  
     
     
         7 . The system of  claim 6 , wherein the one or more gene depositories comprise a biodegradable particle comprising the recombinant virus.  
     
     
         8 . The system of  claim 7 , wherein the biodegradable particle has a half-life of about 1 to 30 days.  
     
     
         9 . The system of  claim 1 , wherein the one or more the gene depositories comprise genetically modified donor cells comprising the expression cassette.  
     
     
         10 . The system of  claim 9 , wherein the genetically modified donor cells are subjected to conditioning in vitro prior to introduction to one or more of the gene depositories.  
     
     
         11 . The system of  claim 1  or  9 , wherein the one or more the gene depositories comprise stem cells, fibroblast cells, vascular endothelial cells or vascular smooth muscle cells.  
     
     
         12 . The system of  claim 1 , wherein the one or more the gene depositories comprise donor cells.  
     
     
         13 . The system of  claim 9  or  12 , wherein modified donor cells are autologous cells.  
     
     
         14 . The system of  claim 1 , wherein at least one of the gene regulatory stimulators is within at least one of the gene depositories.  
     
     
         15 . The system of  claim 1 , wherein the gene regulatory stimulator includes an electric current emitter.  
     
     
         16 . The system of  claim 1 , wherein the gene regulatory stimulator comprises one or more light emitters that emit light having predetermined wavelengths and energies, one or more speakers that emit acoustic energy, one or more thermal radiators that emit thermal energy, one or more electric field generators that emit an electric field, one or more drug delivery devices that contain a chemical agent, or any combination thereof.  
     
     
         17 . The system of  claim 1 , wherein the lead includes one or more lumens adapted for delivery of virus or cells to one or more of the gene depositories.  
     
     
         18 . The system of  claim 1 , wherein the material includes polysulfone, polyethersulfone, polyvinylidene fluoride, polypropylene or regenerated cellulose.  
     
     
         19 . The system of  claim 1 , wherein the material is selected to allow passage of virus.  
     
     
         20 . The system of  claim 1 , further comprising a fiber optic wave guide disposed along the lead, and a light source disposed within a header associated with the lead.  
     
     
         21 . A lead comprising: 
 a lead body extending from a proximal end portion to a distal end portion and having an intermediate portion therebetween;    one or more gene depositories disposed along the lead body, the one or more gene depositories include a porous, biocompatible and substantially nonbiodegradable material, wherein the material is selected to allow the passage of soluble cellular factors and prevent passage of cells across the material;    the one or more gene depositories having at least one of a recombinant virus comprising an expression cassette comprising a regulatable transcription control element operably linked to an open reading frame of interest, genetically modified donor cells comprising an expression cassette comprising a regulatable transcription control element operably linked to an open reading frame of interest, donor cells which are not genetically modified but which comprise an endogenous gene which includes a regulatable transcription control element operably linked to an open reading frame of interest, or a combination thereof; and    one or more gene regulatory stimulators associated with the one or more gene depositories, the one or more gene regulatory stimulators emit a regulatory stimulation capable of regulating the regulatable transcription control element.    
     
     
         22 . The lead of  claim 21 , wherein the donor cells are stem cells, fibroblast cells, or vascular cells.  
     
     
         23 . The lead of  claim 21 , wherein the gene regulatory stimulator comprises at least one of a generator which emits an electric current, one or more light emitters that emit light having predetermined wavelengths and energies, one or more speakers that emit acoustic energy, one or more thermal radiators that emit thermal energy, one or more electric field generators that emit an electric field, or one or more drug delivery devices that contain a chemical agent.  
     
     
         24 - 46 . (canceled)