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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

AAV2/1-TNFR:Fc gene delivery prevents periodontal disease progression

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Author(s):
Cirelli, J. A. [1] ; Park, C. H. [1, 2] ; MacKool, K. [1] ; Taba, Jr., M. [1] ; Lustig, K. H. [3] ; Burstein, H. [4] ; Giannobile, W. V. [1, 2]
Total Authors: 7
Affiliation:
[1] Univ Michigan, Sch Dent, Dept Periodont & Oral Med, Ann Arbor, MI 48109 - USA
[2] Univ Michigan, Dept Biomed Engn, Ann Arbor, MI 48109 - USA
[3] VLST Corp, Seattle, WA - USA
[4] Targeted Genetics Corp, Dept Res, Seattle, WA - USA
Total Affiliations: 4
Document type: Journal article
Source: Gene Therapy; v. 16, n. 3, p. 426-436, MAR 2009.
Web of Science Citations: 34
Abstract

Periodontal disease is a chronic inflammatory condition induced by tooth-associated microbial biofilms that induce a host immune response. Therapeutic control of progressive tissue destruction in high-risk patients is a significant challenge in therapy. Soluble protein delivery of antagonists to tumor necrosis factor-alpha (TNF-alpha) inhibits alveolar bone resorption due to periodontitis. However, protein therapy raises several concerns, such as recurrence of disease activity after treatment cessation and repeated dosing regimens. In this study, we used pseudotyped adeno-associated virus vector based on serotype 1 (AAV2/1) to deliver the TNF receptor-immunoglobulin Fc (TNFR:Fc) fusion gene to rats subjected to experimental Porphyromonas gingivalis (Pg)-lipopolysaccharide (LPS)-mediated bone loss. Animals received Pg-LPS delivered to the gingivae thrice weekly for 8 weeks, vehicle alone, Pg-LPS and intramuscular delivery of pseudotyped AAV2/1-TNFR:Fc vector (1 x 10(11) DNase I-resistant particles) or AAV2/1-TNFR:Fc vector delivered to naive animals. AAV2/1-TNFR:Fc therapy led to sustained therapeutic levels of serum TNFR protein and protected against Pg-LPS-mediated loss of bone volume and density. Furthermore, AAV2/1-TNFR:Fc administration reduced local levels of multiple proinflammatory cytokines and osteoclast-like cells at the periodontal lesions. These findings suggest that delivery of AAV2/1-TNFR:Fc may be a viable approach to modulate periodontal disease progression. (AU)

FAPESP's process: 06/01970-0 - Genetic therapy with adeno-associated virus encoding tumor necrosis factor receptor for the treatment of periodontitis
Grantee:Joni Augusto Cirelli
Support type: Scholarships abroad - New Frontiers