Devices and methods for treatment of ocular disorders through delivery of therapeutic nucleic acids

Abstract

Several embodiments disclosed herein relate to the delivery of therapeutic nucleic acids to an ocular tissue in order to provide a therapeutic effect to reduce symptoms of or otherwise alleviate an ocular disorder. In particular embodiments, plasmid DNA is delivered to the cells of the trabecular meshwork in order to ameliorate increasing intraocular pressure. Devices and systems to accomplish this delivery are also disclosed.

1 .- 20 . (canceled) 
     
     
         21 . A device for generating and applying an electrical field to an ocular target tissue, the device comprising:
 a first arcuate housing comprising one or more positive electrodes; and   a second arcuate housing comprising one or more negative electrodes,   wherein the first and second arcuate housings are adjustable with respect to one another to form on a single plane at least a portion of a single ovoid shape of a desired dimension, wherein the first arcuate housing forms a first arcuate portion of the single ovoid shape and the second arcuate housing forms a second arcuate portion of the single ovoid shape, and wherein the desired dimension is adjustable to substantially correspond to a shape of an outer surface of an eye of a subject.   
     
     
         22 . The device of  claim 21 , wherein the one or more positive electrodes and the one or more negative electrodes are equal in number. 
     
     
         23 . The device of  claim 21 , further comprising:
 a control module configured to receive user input related to a percentage or number of the one or more positive and the one or more negative electrodes to be activated during application of the electrical field to a specific ocular target tissue.   
     
     
         24 . The device of  claim 21 , wherein the ocular target tissue comprises a trabecular meshwork and the electrical field is applied at a voltage between 100 mV and 100 V, wherein the electric field is pulsed between 1 and 20 pulses, wherein the pulses are applied for a duration of between 0.5 and 10 milliseconds per pulse, and wherein the pulses are separated by an interval of between about 20 to 150 milliseconds. 
     
     
         25 . The device of  claim 21 , further comprising a pressure transducer configured to assess an intraocular pressure of an anterior chamber of the eye of the subject. 
     
     
         26 . The device of  claim 21 , further comprising an injection system for delivery of a therapeutic agent to a specific ocular target tissue. 
     
     
         27 . The device of  claim 26 , wherein the therapeutic agent comprises a polynucleotide encoding lysyl oxidase-like 1 (LOXL1), CYP1B1, myocilin, TGF-beta latency-associated peptide (LAP), prostaglandin F synthase, C3 transferase, caldesmon or variants thereof. 
     
     
         28 . The device of  claim 26 , wherein the device is configured to deliver the therapeutic agent in a volume of about 10 to about 1000 microliters, and at a concentration between about 10 micrograms nucleic acid per milliliter to 5000 micrograms per milliliter. 
     
     
         29 . The device of  claim 26 , wherein the device is configured to deliver the therapeutic agent at a rate between about 0.1 microliters per minute and about 100 microliters per minute. 
     
     
         30 . The device of  claim 26 , wherein the device is configured to deliver the therapeutic agent at a pressure between about 10 and about 40 mm of mercury. 
     
     
         31 . The device of  claim 26 , wherein the injection system comprises one or more syringes or other injection devices. 
     
     
         32 . The device of  claim 31 , wherein the one or more syringes or other injection devices are rotatable. 
     
     
         33 . The device of  claim 26 , wherein the injection system comprises:
 a first syringe configured to deliver the therapeutic agent to an anterior chamber of the eye of the subject; and   a second syringe configured to withdraw aqueous humor from the anterior chamber of the eye of the subject.   
     
     
         34 . The device of  claim 33 , wherein the volume of aqueous humor withdrawn is equivalent to the volume of therapeutic agent delivered, and the withdrawal of aqueous humor is performed prior to delivery of the therapeutic agent. 
     
     
         35 . The device of  claim 21 , further comprising:
 an injection system for delivery of a therapeutic agent to a specific ocular target tissue; and   a pressure transducer configured to assess an intraocular pressure of an anterior chamber of the eye of the subject.   
     
     
         36 . The device of  claim 35 , wherein one or more of a volume, a concentration, a rate, a frequency, or a pressure of the delivery of the therapeutic agent is selected based at least in part on the assessed intraocular pressure of the anterior chamber. 
     
     
         37 . The device of  claim 21 , wherein the one or more positive electrodes and the one or more negative electrodes are replaceable. 
     
     
         38 . The device of  claim 21 , wherein the device is configured to apply an electrical field focused on a trabecular meshwork of the eye of the subject. 
     
     
         39 . The device of  claim 21 , wherein the device is configured to apply an electrical field focused on a ciliary body of the eye of the subject. 
     
     
         40 . The device of  claim 21 , wherein the device is configured to facilitate delivery of a therapeutic agent to a specific ocular target tissue, wherein the therapeutic agent comprises a plasmid.