Uveal melanoma commonly known as ocular or choroidal melanoma, is a rare cancer of the eye. It is an intraocular malignancy that arises from melanocytes of the choroid, ciliary body, and iris of the eye. Ocular melanoma is diagnosed in approximately 2,000-2,500 adults annually in the United States. In both the U.S. and Europe, this equates to about 5 - 7.5 cases per million people per year and, for people over 50 years old, the incidence rate increases to around 21 per million per year. While the primary tumor is highly treatable, about half of the patients will develop metastasis —typically to the liver. Metastatic disease is universally fatal. While traditional staging methods such as tumor size and location, still play a role in assessing metastatic risk, they are rarely used to individualize patient management plans. Newer methods include chromosomal gene expression analysis, yet these methods have their technical limitations. Clearly, what is needed is a better, cheaper and reproducible prognostic test.

Ocular degenerative diseases including age-related macular degeneration (AMD), retinitis pigmentosa, glaucoma, and corneal endothelial dystrophy (CED) cause irreversible vision loss and affect millions of people worldwide. Currently, there is no effective drug intervention. Grafting healthy eye cells to replenish the diseased tissues such as retina represents a promising therapeutic approach. However, previous attempts at using primary human eye cells have met with limited success due to the limited expansion capacity and differentiation potential of adult progenitors or difficulty of obtaining sufficient human fetal retinal progenitors, and possible ethical concerns. Human pluripotent stem cells (PSCs), including human embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs) represent promising renewable donor sources for cell-based replacement therapy. Nevertheless, PSCs themselves are not suitable for direct transplantation in clinical applications due to their tendency to form teratomas and low efficiency in repopulating host tissues with desirable reprogrammed cell types in vivo. While the advancement of clinical trials of hESC-derived RPE transplants for treatment of patients with Stargardt's macular dystrophy and AMD is encouraging to the field, there is a great need for methods of generating unlimited other specialized eye cells effectively in vitro for treating blindness due to the loss of photoreceptors, RGCs and CECs. Therefore, there is a major interest in development of in vitro expandable cell sources for engineering corneal endothelium.

Glaucoma is a condition in which intraocular pressure (IOP) causes damage to the optic nerve and progressively leads to permanent loss of vision.  The diagnosis and monitoring of glaucoma requires regular measurements of patients’ IOP.  The standard ocular tonometry techniques currently used in a clinical practice provide only a snapshot of the IOP profile and usually with readings taken weeks or months apart.  More recently, there have been implantable sensors under development that enable long term and continuous IOP monitoring.  However, each has drawbacks in one or more of the following concerns: signal readout, size, sensitivity, power consumption, special instrumentation requirement, and/or complex fabrication processes.

This invention provides microRNA therapeutics that augment blood vessel growth, which may have application for indications where it is desired to reduce or stimulate angiogenesis. Reducing or inhibiting angiogenesis may be useful for indications such as degenerative eye diseases and cancer. Stimulating blood vessel growth may be useful for treating indications such as cardiovascular, thrombotic or ischemic diseases. Cells lining blood vessels are usually among the least proliferative cell types, but this desired quiescence may be interrupted in response to growth factors during pathological neovascularization manifested in disease states such as macular degeneration and cancer. MicroRNAs are known to be key regulators of angiogenesis and specific miRNAs have been found to be effective toward these indications.

Brief description not available

Amyloids are insoluble fibrous protein aggregates that accumulate in various organs throughout the human body. It has been clinically proven that abnormal accumulation of beta-amyloids in the brain is associated with various neurodegenerative diseases, including Alzheimer disease. Diagnostic biomarkers currently in clinical development are limited to small radio-labeled molecules for detection of amyloidosis through PET or SPECT imaging modes. There remains a pressing need for the design and development of new imaging agents for conclusive early diagnosis of Alzheimer’s disease, ideally through widely accessible detection platforms.

Brief description not available

The treatment of eye diseases, such as age-related macular degeneration, diabetic retinopathy, uveitis, and others, has been problematic. The largest barrier to effective treatment is the difficulty of delivering the appropriate concentration of drug to the correct location in the eye for a sufficient length of time. Various solutions have been attempted, including repeated intraocular injections of drug or surgical implantation of drug-permeated material. However, these methods are impractical and present a significant risk to the patient: multiple injections are required, each carrying a finite risk of infection, and surgical procedures are cumbersome and not always effective.

Brief description not available

Target-selective drug delivery remains a challenge for various therapeutic applications and particularly for cancer. Current targeting strategies include formulation and encapsulation for preferential release in the acidic tumor environment as well as covalent conjugation via linkers sensitive to pH, to oxygen levels, or to disease-specific enzymes. These approaches have been limited by: Stringent requirements on linkable drugs and carriers.Inflexible rates of release.Insufficient target/tumor-specificity of relevant enzymes.