h no gene expression, except for the latency associated transcript gene (LAT). The role of LAT during latency is still not well understood. The LAT gene may be the key to understand the mechanism of HSV-1 or HSV-2 latency reactivation. The purpose of the research outlined in this proposal is to investigate LAT gene of this novel herpesvirus. To accomplish this we will sequence and annotate the genomes of LHV-4 and characterize the LAT region. Because of its close relationship to the primate virus lineage, and its ability to infect rabbits, information on latency in this virus may provide a natural host model system for understanding latency in herpesvirus infections of humans. PUBLIC HEALTH RELEVANCE: In this research application we propose to sequence the genome of a recently discovered Simplex herpesvirus pathogenic for rabbits that is closely related to HSV-1 and 2. The goal of this research is to characterize the latency associated transcript gene (LAT) region and investigate the role of LAT during latency in a natural host model system. .

We wish to improve treatment for patients with deep-seated brain tumors. With the help of the MRI-guided and nanoparticle-enabled system we are constructing, therapeutic access to these tumors will be provided through the delicate nooks, crannies, and membranes of the skull. In preliminary studies, we have demonstrated the ability to bypass the blood-brain barrier traumatically and to manipulate magnetic nanoparticles (MNPs) in mouse brains. By the end of Phase I, we will have built and tested an MRI-compatible gradient insert system capable of delivering magnetic nanoparticles (MNPs) to selected regions in normal mouse brains. Using the data collected from the Phase I mouse study, we will have run simulations of a large-scale magnetic insert system, in order to demonstrate the feasibility of targeting deep- seated brain and skull-base targets in humans. Discussions are well underway with investors to match the Phase II NCI contribution (see Letter of Support). Strategic p