Genetic therapy with adeno-associated virus encoding tumor necrosis factor receptor for the treatment of periodontitis

• Grant number: 06/01970-0
• Support Opportunities: Scholarships abroad - New Frontiers
• Start date: August 01, 2006
• End date: July 24, 2007
• Field of knowledge: Health Sciences - Dentistry
• Principal Investigator: Joni Augusto Cirelli
• Grantee: Joni Augusto Cirelli
• Host Investigator: William Victor Gianobille
• Host Institution: Faculdade de Odontologia (FOAr). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
• Institution abroad: University of Michigan, United States

Abstract

The pathogenesis of the periodontal disease is represented by a host inflammatory response to periodontal pathogens of the oral biofilm. Cytokines such as tumor necrosis factor alpha (TNF) are produced within periodontal tissues and trigger irreversible tissue destruction. Host modulation therapies blocking the activity of pro-inflammatory cytokines are promising in periodontal treatment. The purpose of this study is determine the efficacy of gene delivery of Tumoral Necrosis Factor Receptor (TNFR:Fc) by an adeno-associated virus in preventing alveolar bone loss in an experimental animal model of periodontitis. Periodontal disease will be induced in rats by ligatures placed in a submarginal position around the cervix of 1st and 2nd maxillary molars, on both sides. The genetic vector will be delivered by a single intramuscularly injection in the quadriceps muscle (systemic delivery) or in the papillary gingival tissue around the maxillary molars (local administration). Control groups will be injected with vehicle solution or will receive ligature only. The injections will be performed five weeks before disease induction. Five animals per group/period will be sacrificed one, two or three weeks after ligatures placement. Endpoints includes: TNFR:Fc concentration in the serum, quantitative alveolar bone loss around maxillary molars and pro-inflammatory cytokines expression by periodontal tissues of theses teeth. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

CIRELLI, J. A.; PARK, C. H.; MACKOOL, K.; TABA, JR., M.; LUSTIG, K. H.; BURSTEIN, H.; GIANNOBILE, W. V.. AAV2/1-TNFR:Fc gene delivery prevents periodontal disease progression. Gene Therapy, v. 16, n. 3, p. 426-436, MAR 2009. (06/01970-0)