Post-transcriptional gene silencing with RNA interference (RNAi) as an antiviral therapy for rabies

• Grant number: 13/05884-4
• Support Opportunities: Regular Research Grants
• Start date: August 01, 2013
• End date: July 31, 2015
• Field of knowledge: Biological Sciences - Microbiology - Applied Microbiology
• Principal Investigator: Paulo Eduardo Brandão
• Grantee: Paulo Eduardo Brandão
• Host Institution: Faculdade de Medicina Veterinária e Zootecnia (FMVZ). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Rabies is a 100% lethal zoonosis and is still a burden for Public Health. The current protocol for the treatment of human rabies is based on antivirals such as ketamin, ribavirin, midazolam and amantadin, but the lack of its reproducibility in human patients is a current problem. The aims of this project are to test in vitro in BHK-21 cells anti-rabies virus protocols based on RNA interference (RNAi) using short-interfering RNAs (siRNAs) targeting rabies virus leader RNA and also the mRNA for the nucleoprotein (N), using the PV fixed rabies virus strain and two field strains, one isolated from a dog and one from cattle, with a range of lethal doses and different transfection protocols and next to apply the more efficient protocol in mice using the three rabies virus strains per transcranial delivery of siRNAs, measuring the inhibition efficiency both in vivo and in vitro with direct immunofluorescence and quantitative PCR for N mRNA, besides the evaluation of possible toxic effects using a quantitative PCR for the Beta-actin mRNA. It's expected these antivirals can be associated to those already available in order to improve the treatment of rabies patients and to decrease the lethality of the disease. (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)

DURYMANOVA ONO, EKATERINA ALEXANDROVNA; TANIWAKI, SUELI AKEMI; BRANDAO, PAULO. Short interfering RNAs targeting a vampire-bat related rabies virus phosphoprotein mRNA. Brazilian Journal of Microbiology, v. 48, n. 3, p. 566-569, JUL-SEP 2017. (11/00439-7, 13/05884-4)