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

a nucleic acid and ocular disease technology, applied in the field of eye treatment systems, can solve the problems of patients who use eye drops and/or medication for treatment, many unwanted and/or unintended side effects, and doctors may not be able to efficiently control eye disease, so as to achieve the effect of maximizing the amount of plasmid dna

Inactive Publication Date: 2019-03-21
DOHENY EYE INST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

The patent describes a method for delivering a therapeutic agent to the eye by withdrawing aqueous humor from the eye and then delivering the agent. The volume of aqueous humor withdrawn can equal or exceed the amount of therapeutic agent delivered. The delivery and withdrawal can be performed in any order, and the withdrawal can be at a different site from the delivery. The concentration, rate, and pressure of delivery can be selected based on intraocular pressure. The therapeutic agent can be delivered in a volume of 10 to 10,000 microliters and can be repeated removed and replaced with a solution containing the plasmid DNA to maximize the amount of DNA delivered. The technical effects include a minimized amount of damage to the corneal endothelium, reduced risk of inflammation, and an improved safety profile.

Problems solved by technology

However, patients who use eye drops and / or medication for treatment may experience several unwanted and / or unintended discomfort or other side effects.
Additionally, even with surgery, doctors may not be able to efficiently control eye disease.
After typical surgery, patients may also face several complications and risks, such as eye pressure that is too high or low, inflammation, discomfort, and / or scarring.

Method used

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

Examples

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Effect test

example 1

Electroporation-Assisted Delivery of Nucleic Acid to the Trabecular Meshwork

[0152]This example relates to non-viral electroporation-assisted transfection as a way of delivering genes to the trabecular meshwork (TM). As discussed above, the TM lies immediately adjacent to the ocular surface externally and anterior chamber internally. The TM is bathed by aqueous humor. Aqueous humor, being a physiological salt solution, serves as an excellent ionic conductor. The aqueous-filled anterior chamber represents a depot into which a gene or DNA may be deposited by trans-corneal injection, perfusion, etc., as is disclosed above. Within this space, exogenous DNA mixes with aqueous humor to then bathe TM cells. To facilitate delivery of the gene of interest to the TM cells, application of an electric field can be used. The TM, being immediately adjacent to the ocular surface, is readily accessible by surface electrodes that are used to generate an electric field across the tissue, thereby makin...

example 2

Naked DNA Delivery to the Trabecular Meshwork to Treat Glaucoma

[0162]Exfoliation glaucoma (XFG), a common glaucoma variant, is incurable and associated with aggressive vision loss, volatile intraocular pressure (TOP) and single nucleotide polymorphisms (SNPs) of the lysyl oxidase-like 1 (LOXL1) gene. The present example aims to identify a cure or long-term relief from XFG by correction of the molecular defects in tissues responsible for abnormal IOP.

[0163]While, viral vectors are used to efficiently deliver genes to tissues in animal models, their use for human gene therapy has been limited by immunogenic and safety risks, including fatality. Non-viral naked plasmid DNA (pDNA) does not carry these risks, however, and it is simpler to use. The systems, methods and devices disclosed herein relate to the use of pDNA as a safe and effective vector for human glaucoma gene therapy.

[0164]The trabecular meshwork (TM) is a key tissue regulator of IOP located at the exit of the anterior chamb...

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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.

Description

RELATED CASES[0001]This application is a continuation of U.S. patent application Ser. No. 15 / 335,324, filed on Oct. 26, 2016, which claims the benefit of U.S. Provisional Patent Application No. 62 / 249,143, filed on Oct. 30, 2015. Each of the foregoing applications is hereby incorporated herein by reference in its entirety.BACKGROUNDField[0002]Several embodiments of the present disclosure generally relate to eye treatment systems, and more particularly to systems, devices, and methods for treatment of ocular disorders through the delivery of therapeutic nucleic acids.Description of the Related Art[0003]As many ocular disorders remain incurable, it is important to develop technology systems for treating such disorders. For example, glaucoma is an ocular disorder that destroys retinal ganglion cells and their axons causing a corresponding loss of vision. Elevated intraocular pressure, either through increased production or decreased outflow of aqueous humor, is associated with glaucoma...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61F9/007A61F9/00A61N1/08A61N1/32A61K9/00A61B3/16A61K31/713A61N1/04A61K41/00
CPCA61B3/16A61K41/0047A61N1/327A61F9/0008A61N1/0424A61K31/713A61F9/0026A61N1/0472A61F9/0017A61K9/0048A61N1/32A61N1/08A61F9/00781
Inventor TAN, CHEE HIAN
Owner DOHENY EYE INST
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