AAV2/1-TNFR:Fc Gene Delivery Prevents Periodontal Disease Progression

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 tum...

Descripción completa

Detalles Bibliográficos
Autores principales: Cirelli, Joni A, Park, Chan Ho, MacKool, Kathryn, Taba, Mario, Lustig, Kurt H, Burstein, Haim, Giannobile, William V
Formato: Texto
Lenguaje:English
Publicado: 2008
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656404/
https://www.ncbi.nlm.nih.gov/pubmed/19078994
http://dx.doi.org/10.1038/gt.2008.174
_version_ 1782165501291528192
author Cirelli, Joni A
Park, Chan Ho
MacKool, Kathryn
Taba, Mario
Lustig, Kurt H
Burstein, Haim
Giannobile, William V
author_facet Cirelli, Joni A
Park, Chan Ho
MacKool, Kathryn
Taba, Mario
Lustig, Kurt H
Burstein, Haim
Giannobile, William V
author_sort Cirelli, Joni A
collection PubMed
description 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-α) 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 (1×10(11) DNase I-resistant particles) or AAV2/1-TNFR:Fc vector delivered to naïve 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 pro-inflammatory 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.
format Text
id pubmed-2656404
institution National Center for Biotechnology Information
language English
publishDate 2008
record_format MEDLINE/PubMed
spelling pubmed-26564042009-09-01 AAV2/1-TNFR:Fc Gene Delivery Prevents Periodontal Disease Progression Cirelli, Joni A Park, Chan Ho MacKool, Kathryn Taba, Mario Lustig, Kurt H Burstein, Haim Giannobile, William V Gene Ther Article 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-α) 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 (1×10(11) DNase I-resistant particles) or AAV2/1-TNFR:Fc vector delivered to naïve 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 pro-inflammatory 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. 2008-12-11 2009-03 /pmc/articles/PMC2656404/ /pubmed/19078994 http://dx.doi.org/10.1038/gt.2008.174 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Cirelli, Joni A
Park, Chan Ho
MacKool, Kathryn
Taba, Mario
Lustig, Kurt H
Burstein, Haim
Giannobile, William V
AAV2/1-TNFR:Fc Gene Delivery Prevents Periodontal Disease Progression
title AAV2/1-TNFR:Fc Gene Delivery Prevents Periodontal Disease Progression
title_full AAV2/1-TNFR:Fc Gene Delivery Prevents Periodontal Disease Progression
title_fullStr AAV2/1-TNFR:Fc Gene Delivery Prevents Periodontal Disease Progression
title_full_unstemmed AAV2/1-TNFR:Fc Gene Delivery Prevents Periodontal Disease Progression
title_short AAV2/1-TNFR:Fc Gene Delivery Prevents Periodontal Disease Progression
title_sort aav2/1-tnfr:fc gene delivery prevents periodontal disease progression
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2656404/
https://www.ncbi.nlm.nih.gov/pubmed/19078994
http://dx.doi.org/10.1038/gt.2008.174
work_keys_str_mv AT cirellijonia aav21tnfrfcgenedeliverypreventsperiodontaldiseaseprogression
AT parkchanho aav21tnfrfcgenedeliverypreventsperiodontaldiseaseprogression
AT mackoolkathryn aav21tnfrfcgenedeliverypreventsperiodontaldiseaseprogression
AT tabamario aav21tnfrfcgenedeliverypreventsperiodontaldiseaseprogression
AT lustigkurth aav21tnfrfcgenedeliverypreventsperiodontaldiseaseprogression
AT bursteinhaim aav21tnfrfcgenedeliverypreventsperiodontaldiseaseprogression
AT giannobilewilliamv aav21tnfrfcgenedeliverypreventsperiodontaldiseaseprogression