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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

Texto completo
Autor(es):
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]
Número total de Autores: 7
Afiliação do(s) autor(es):
[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
Número total de Afiliações: 4
Tipo de documento: Artigo Científico
Fonte: Gene Therapy; v. 16, n. 3, p. 426-436, MAR 2009.
Citações Web of Science: 34
Resumo

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)

Processo FAPESP: 06/01970-0 - Terapia genética com vírus adeno-associado codificando gene de receptor de fator de necrose tumoral no tratamento da periodontite
Beneficiário:Joni Augusto Cirelli
Linha de fomento: Bolsas no Exterior - Novas Fronteiras