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Swarms of chemically modified antiviral siRNA targeting herpes simplex virus infection in human corneal epithelial cells.
Kalke, Kiira; Lund, Liisa M; Nyman, Marie C; Levanova, Alesia A; Urtti, Arto; Poranen, Minna M; Hukkanen, Veijo; Paavilainen, Henrik.
Afiliação
  • Kalke K; Institute of Biomedicine, University of Turku, Turku, Finland.
  • Lund LM; Institute of Biomedicine, University of Turku, Turku, Finland.
  • Nyman MC; Institute of Biomedicine, University of Turku, Turku, Finland.
  • Levanova AA; Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
  • Urtti A; School of Pharmacy, University of Eastern Finland, Kuopio, Finland.
  • Poranen MM; Faculty of Pharmacy, University of Helsinki, Helsinki, Finland.
  • Hukkanen V; Molecular and Integrative Biosciences Research Programme, Faculty of Biological and Environmental Sciences, University of Helsinki, Helsinki, Finland.
  • Paavilainen H; Institute of Biomedicine, University of Turku, Turku, Finland.
PLoS Pathog ; 18(7): e1010688, 2022 07.
Article em En | MEDLINE | ID: mdl-35793357
Herpes simplex virus type 1 (HSV-1) is a common virus of mankind and HSV-1 infections are a significant cause of blindness. The current antiviral treatment of herpes infection relies on acyclovir and related compounds. However, acyclovir resistance emerges especially in the long term prophylactic treatment that is required for prevention of recurrent herpes keratitis. Earlier we have established antiviral siRNA swarms, targeting sequences of essential genes of HSV, as effective means of silencing the replication of HSV in vitro or in vivo. In this study, we show the antiviral efficacy of 2´-fluoro modified antiviral siRNA swarms against HSV-1 in human corneal epithelial cells (HCE). We studied HCE for innate immunity responses to HSV-1, to immunostimulatory cytotoxic double stranded RNA, and to the antiviral siRNA swarms, with or without a viral challenge. The panel of studied innate responses included interferon beta, lambda 1, interferon stimulated gene 54, human myxovirus resistance protein A, human myxovirus resistance protein B, toll-like receptor 3 and interferon kappa. Our results demonstrated that HCE cells are a suitable model to study antiviral RNAi efficacy and safety in vitro. In HCE cells, the antiviral siRNA swarms targeting the HSV UL29 gene and harboring 2´-fluoro modifications, were well tolerated, induced only modest innate immunity responses, and were highly antiviral with more than 99% inhibition of viral release. The antiviral effect of the 2'-fluoro modified swarm was more apparent than that of the unmodified antiviral siRNA swarm. Our results encourage further research in vitro and in vivo on antiviral siRNA swarm therapy of corneal HSV infection, especially with modified siRNA swarms.
Assuntos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Herpesvirus Humano 1 / Herpes Simples Idioma: En Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Herpesvirus Humano 1 / Herpes Simples Idioma: En Ano de publicação: 2022 Tipo de documento: Article