The formulations core will be led by Southwest Research Institute, a commercial entity with expertise in formulating drug for mucosal delivery. The singular purpose of this Core will be to develop a nanocapsular formulation of short interfering RNA (siRNA) that will be appropriate for mucosal delivery. To accomplish this goal, various nanocapsular formulations will be synthesized and tested for their ability to incorporate and deliver siRNA to the cellular cytoplasm;Initial experiments will use a siRNA molecule conjugated to a fluorophore, this allowing rapid microscopic evaluation of the efficiency of cellular entry. Once an optimum formulation is identified, this Core will produce formulations of siRNA targeting macaque CCR5 and enhanced green fluorescent protein in year 1. These products will be supplied to Projects by Ramratnam and Lambert for in vitro and in vivo evaluations of gene silencing potency and toxicity. These evaluations will allow us to decide upon an optimum formulation conditions that will be used to formulate siRNAs identified by Projects by Herold and Lambert in future years of the grant.
| Song Gao, Jin; Zhang, Yingjie; Li, Ming et al. (2010) Atypical transcription of microRNA gene fragments. Nucleic Acids Res 38:2775-87 |
| Cheshenko, Natalia; Trepanier, Janie B; Segarra, Theodore J et al. (2010) HSV usurps eukaryotic initiation factor 3 subunit M for viral protein translation: novel prevention target. PLoS One 5:e11829 |
| LaFrance Jr, W C; Keitner, G I; Papandonatos, G D et al. (2010) Pilot pharmacologic randomized controlled trial for psychogenic nonepileptic seizures. Neurology 75:1166-73 |
| Huang, Hao-Shun; Buck, Christopher B; Lambert, Paul F (2010) Inhibition of gamma secretase blocks HPV infection. Virology 407:391-6 |
| Wilson, Sarah S; Fakioglu, Esra; Herold, Betsy C (2009) Novel approaches in fighting herpes simplex virus infections. Expert Rev Anti Infect Ther 7:559-68 |
| Cheshenko, Natalia; Liu, Wen; Satlin, Lisa M et al. (2007) Multiple receptor interactions trigger release of membrane and intracellular calcium stores critical for herpes simplex virus entry. Mol Biol Cell 18:3119-30 |
