Compositions comprising fluorescent dyes associated with viral components for nerve imaging

Abstract

Disclosed herein is a composition for imaging nerve cells. The composition includes a fluorescent dye; and a viral component including a neurotropic herpes varicellae unable to replicate in nerve cells, a viral protein of a neurotropic herpes varicellae unable to replicate in nerve cells, a capsid of a neurotropic herpes varicellae unable to replicate in nerve cells, or a combination thereof. The fluorescent dye is bound to the viral component to form a dye/viral component complex that is capable of penetrating nerve cells.

1 . A composition comprising:
 a fluorescent dye; and   a viral component comprising a neurotropic herpes varicellae unable to replicate in nerve cells, a viral protein of a neurotropic herpes varicellae unable to replicate in nerve cells, a capsid of a neurotropic herpes varicellae unable to replicate in nerve cells, or a combination thereof;   wherein the fluorescent dye is bound to the viral component to form a dye/viral component complex that is capable of penetrating nerve cells.   
     
     
         2 . The composition according to  claim 1 , wherein the fluorescent dye is indocyanine green, infracyanine green, green fluorescent dye, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde, fluorescamine, Rose Bengal, trypan blue, fluoro-gold, 3-indocyanine green-acyl-1,3-thiazolidine-thione, green fluorescent protein, red fluorescent protein, yellow fluorescent protein, blue fluorescent protein, or a combination thereof. 
     
     
         3 . The composition according to  claim 2 , wherein the fluorescent dye is indocyanine green. 
     
     
         4 . The composition according to  claim 1 , wherein the viral component is a neurotropic herpes varicellae that is derived from HSV-2. 
     
     
         5 . The composition according to  claim 4 , wherein the neurotropic herpes varicellae comprises HSV-2 IPC10ΔRR. 
     
     
         6 . The composition according to  claim 1 , wherein the neurotropic herpes varicellae is rendered unable to replicate in nerve cells by mutation, UV radiation, chemical treatment, or heat treatment. 
     
     
         7 . A method of making the composition according to  claim 1 , comprising:
 combining the fluorescent dye with the viral component; and   allowing the fluorescent dye to be bound to the viral component to form a dye/viral component complex that is capable of penetrating nerve cells.   
     
     
         8 . The method according to  claim 7 , wherein the neurotropic herpes varicellae is rendered unable to replicate in nerve cells by mutation, UV radiation, chemical treatment, or heat treatment. 
     
     
         9 . A method for reducing the risk of iatrogenic injury to a subject during a surgical procedure, comprising:
 (a) administering the composition according to  claim 1  to the subject;   (b) allowing the dye/viral component complex to penetrate nerve cells;   (c) applying a sufficient amount of radiant energy to the subject such that the dye fluoresces;   (d) intraoperatively obtaining a fluorescence image of the subject; and   (e) observing the fluorescence image to determine the location of one or more nerves in the subject.   
     
     
         10 . The method according to  claim 9 , wherein the fluorescent dye is indocyanine green, infracyanine green, green fluorescent dye, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde, fluorescamine, Rose Bengal, trypan blue, fluoro-gold, 3-indocyanine green-acyl-1,3-thiazolidine-thione, green fluorescent protein, red fluorescent protein, yellow fluorescent protein, blue fluorescent protein, or a combination thereof. 
     
     
         11 . The method according to  claim 10 , wherein the fluorescent dye is indocyanine green. 
     
     
         12 . The method according to  claim 9 , wherein the viral component is a neurotropic herpes varicellae that is derived from HSV-2. 
     
     
         13 . The method according to  claim 12 , wherein the neurotropic herpes varicellae comprises HSV-2 IPC10ΔRR. 
     
     
         14 . A method for diagnosing a nerve condition in a subject, comprising:
 (a) administering the composition according to  claim 1  to the subject;   (b) allowing the dye/viral component complex to penetrate nerve cells;   (c) applying a sufficient amount of radiant energy to the subject such that the dye fluoresces;   (d) intraoperatively obtaining a fluorescence image of the subject; and   (e) observing a nerve in the fluorescence image to determine whether the nerve is transected.   
     
     
         15 . The method according to  claim 14 , wherein the fluorescent dye is indocyanine green, infracyanine green, green fluorescent dye, fluorescein isothiocyanate, rhodamine, phycoerythrin, phycocyanin, allophycocyanin, o-phthaldehyde, fluorescamine, Rose Bengal, trypan blue, fluoro-gold, 3-indocyanine green-acyl-1,3-thiazolidine-thione, green fluorescent protein, red fluorescent protein, yellow fluorescent protein, blue fluorescent protein, or a combination thereof. 
     
     
         16 . The method according to  claim 15 , wherein the fluorescent dye is indocyanine green. 
     
     
         17 . The method according to  claim 14 , wherein the viral component is a neurotropic herpes varicellae that is derived from HSV-2. 
     
     
         18 . The method according to  claim 17 , wherein the neurotropic herpes varicellae comprises HSV-2 IPC10ΔRR. 
     
     
         19 . The method according to  claim 11 , wherein:
 the viral component is a neurotropic herpes varicellae unable to replicate in nerve cells; and   the neurotropic herpes varicellae is derived from HSV-2 and comprises HSV-2 ICP1ΔRR.   
     
     
         20 . The method according to  claim 16 , wherein:
 the viral component is a neurotropic herpes varicellae unable to replicate in nerve cells; and   the neurotropic herpes varicellae is derived from HSV-2 and comprises HSV-2 ICP10ΔRR.