Compositions Comprising Fluorescent Dyes Associated With Viral Components For Nerve Imaging
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 ICP10ΔRR.
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.