The Problem

Treatments for inherited retinal diseases are currently limited. Gene therapy has emerged as a strong treatment option. However, difficulties have arisen with these gene therapies. It has been found that an intrathecal injection of adenoassociated viral (AAV) gene therapy vector does not penetrate the anatomical barriers to reach the retina and shows limited transduction to the foveal and peripheral retinal ganglion cells. In addition, intravitreal injections carry concern for inflammatory response with residual virus left in the eye. Thus, there is a need for a more efficient and safer gene delivery method for inherited retina diseases.

The Solution

This invention provides a novel approach that delivers AAV to the pre-retinal surface after removal of the vitreous, accelerates it into the retina with adjuvant insulin coadministration, and then removes the vector 30 minutes later to avoid residual AAV in the eye. It improves transduction while mitigating structural trauma and inflammation. Our research showed that insulin-assisted AAV pre-retinal delivery can transduce outer retina photoreceptors. Retinal integrity and function were retained on optical coherence tomography (OCT) and electroretinography (ERG) respectively. The in vivo murine intravitreal injections, ex vivo murine retinal explant cultures, and in vitro cell culture demonstrated a dose response of AAV transduction efficiency to increasing doses of insulin. The approach of applying pre-retinal, adjuvant-assisted, safe molecular entry into retinal cells could be extended further to non-viral methods, including larger genes than AAV carrying capabilities and gene editing with CRISPR-Cas9 technology

Application

This surgical and insulin-adjuvant hybrid approach can be used to deliver gene therapies for the entire field of inherited retinal diseases

Advantages

• An efficient gene delivery for treating inherited retina diseases without structural trauma and inflammation
• Gene-agnostic application for entire field of inherited retinal diseases by extending further to non-viral methods, including gene editing with CRISPR-Cas9 technology, allowing it to be utilized for genes larger than AAV carrying capacities and gene editing approaches

Seeking opportunities for out-licensing and collaboration