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Development of new therapies for ocular herpesvirus in cats (Winn grant report)

W12-042: Development and in vitro optimization of hydrogels for the delivery of FHV specific siRNAs encapsulated in chitosan nanoparticles, $17,785

Rebecca Wilkes, Scott Lenaghan, Christopher Stephens; University of Tennessee
Feline herpesvirus-1 (FHV-1) typically causes respiratory disease in cats; however, chronic recurrent infections can cause severe eye disease often leading to blindness. Currently there is no effective treatment for these chronic cases. Previous Winn funding has helped investigators design a therapeutic agent, small interfering RNAs (siRNAs), which uses the cell’s own machinery to inhibit viral replication through the targeting of essential herpesvirus genes. Investigators have developed a nanoparticle delivery vehicle composed of chitosan, a nontoxic substance to package these siRNAs for delivery into cells. The goal of this study is to develop a hydrogel, similar to a soft contact lens, for delivery of the nanoparticles. 

The first attempt utilized a polyacrylamide gel, but the delivered antiviral particles did not function to inhibit the virus. Thermogels which are liquid at cooler temperatures and gel-like at body temperature, were then tried. This material has been shown to release the target drug in a sustained manner. When the siRNAs were tried in this delivery system, reduced antiviral activity as well as some toxic effects were seen on feline cells in culture. This led to evaluation of a virus vector for delivery of the antiviral siRNAs. The early studies have been encouraging, with reduction of virus replication occurring in cell culture. It is believed that a combination of these latter two systems may offer the optimal treatment regimen, and this is currently under investigation.

Eventually, it is hoped that a topical system will be developed to allow successful drug uptake and provide extended continuous delivery of the FHV-1 specific siRNAs into corneal cells. This study will potentially lead to development of a product suitable for use in cats’ eyes for treatment of FHV-1. [MK]

See also: Wilkes RP, Ward DA, Newkirk KM, et al. Evaluation of delivery agents used for introduction of small interfering RNAs into feline corneal cells. Am J Vet Res 2013;74:243-247.
Reports on previous grants in this project: MT-007  and MT11-007