MiR 204, miR 211, their anti-miRs, and therapeutic uses of same

Inventors

Miller, Sheldon • Zhang, Congxiao • Maminishkis, Arvydas • Wang, Fei

Assignees

US Department of Health and Human Services

Abstract

Embodiments of the invention provide methods of preventing or treating detrimental epithelial cell proliferation, loss of epithelial cell differentiation, age-related macular degeneration and/or proliferative vitreal retinopathy in an individual comprising administering to an individual in need thereof an effective amount of miR 204, an effective amount of miR 211, or an effective amount of a mixture of miR 204 and miR 211. A further embodiment of the invention provides a method of facilitating the transport of a substance across an epithelium in an individual comprising administrating to an individual an effective amount of anti-miR 204, an effective amount of anti-miR 211, or an effective amount of a mixture of anti-miR 204 and anti-miR 211. Additional embodiments of the invention include pharmaceutical compositions of miR 204 and/or miR 211 and pharmaceutical compositions of anti-miR 204 and/or anti-miR 211.

Core Innovation

The invention provides methods for preventing or treating detrimental epithelial cell proliferation, loss of epithelial cell differentiation, age-related macular degeneration, and proliferative vitreal retinopathy in individuals by administering effective amounts of miR 204, miR 211, or their mixtures. Additionally, the invention includes a method to facilitate transport of substances across epithelia by administering anti-miR 204, anti-miR 211, or their mixtures. Pharmaceutical compositions comprising these miRNAs and anti-miRNAs with acceptable carriers are also part of the invention.

The problem addressed arises from the role of epithelial cells, particularly the retinal pigment epithelium (RPE), in regulating the microenvironment around photoreceptors. Damage to RPE and loss of tight junction integrity contribute to diseases like age-related macular degeneration (AMD) and proliferative vitreal retinopathy (PVR). There is an unmet need for identification of miRNAs and anti-miRNAs that modulate epithelial biological functions to prevent or treat such conditions.

This invention details that administration of miR 204 and miR 211 suppresses detrimental cell proliferation and promotes differentiation, with a focus on retinal and ocular epithelial diseases. Conversely, administration of anti-miR 204 and anti-miR 211 increases epithelial permeability by decreasing transepithelial electrical resistance (TER), facilitating substance transport across epithelia. The invention also elucidates the regulation of tight junction proteins and transcription factors by these miRNAs, establishing their therapeutic potential for conditions involving epithelial dysfunction.

Claims Coverage

The patent includes two independent claims focusing on therapeutic methods involving miR 204 and miR 211 for treatment in the eye, as well as administering these miRNAs for age-related macular degeneration.

The independent claims cover methods of administering miR 204, miR 211, or their combinations for treating detrimental epithelial proliferation, loss of differentiation in ocular tissues, and specifically age-related macular degeneration, demonstrating the therapeutic roles of these miRNAs in eye diseases.

Stated Advantages

Documented Applications