Busca avançada
Ano de início
Entree
(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.)

Intranasal vaccination with messenger RNA as a new approach in gene therapy: Use against tuberculosis

Texto completo
Autor(es):
Mostrar menos -
Lorenzi, Julio C. C. [1] ; Trombone, Ana P. F. [1] ; Rocha, Carolina D. [1] ; Almeida, Luciana P. [1] ; Lousada, Ricardo L. [1] ; Malardo, Thiago [1] ; Fontoura, Isabela C. [1] ; Rossetti, Renata A. M. [1] ; Gembre, Ana F. [1] ; Silva, Aristobolo M. [2] ; Silva, Celio L. [1] ; Coelho-Castelo, Arlete A. M. [1]
Número total de Autores: 12
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Bioquim & Imunol, BR-05508 Sao Paulo - Brazil
[2] Univ Fed Minas Gerais, Inst Ciencias Biol, Dept Morfol, Belo Horizonte, MG - Brazil
Número total de Afiliações: 2
Tipo de documento: Artigo Científico
Fonte: BMC Biotechnology; v. 10, OCT 20 2010.
Citações Web of Science: 18
Resumo

Background: mRNAs are highly versatile, non-toxic molecules that are easy to produce and store, which can allow transient protein expression in all cell types. The safety aspects of mRNA-based treatments in gene therapy make this molecule one of the most promising active components of therapeutic or prophylactic methods. The use of mRNA as strategy for the stimulation of the immune system has been used mainly in current strategies for the cancer treatment but until now no one tested this molecule as vaccine for infectious disease. Results: We produce messenger RNA of Hsp65 protein from Mycobacterium leprae and show that vaccination of mice with a single dose of 10 mu g of naked mRNA-Hsp65 through intranasal route was able to induce protection against subsequent challenge with virulent strain of Mycobacterium tuberculosis. Moreover it was shown that this immunization was associated with specific production of IL-10 and TNF-alpha in spleen. In order to determine if antigen presenting cells (APCs) present in the lung are capable of capture the mRNA, labeled mRNA-Hsp65 was administered by intranasal route and lung APCs were analyzed by flow cytometry. These experiments showed that after 30 minutes until 8 hours the populations of CD11c(+), CD11b(+) and CD19(+) cells were able to capture the mRNA. We also demonstrated in vitro that mRNA-Hsp65 leads nitric oxide (NO) production through Toll-like receptor 7 (TLR7). Conclusions: Taken together, our results showed a novel and efficient strategy to control experimental tuberculosis, besides opening novel perspectives for the use of mRNA in vaccines against infectious diseases and clarifying the mechanisms involved in the disease protection we noticed as well. (AU)

Processo FAPESP: 06/03987-7 - Uso de RNA mensageiro como nova abordagem em terapia gênica ou modelos vacinais contra tuberculose
Beneficiário:Arlete Aparecida Martins Coelho-Castelo
Linha de fomento: Auxílio à Pesquisa - Regular