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Durable protection from Herpes Simplex Virus-2 transmission following intravaginal application of siRNAs targeting both a viral and host gene.

Abstract：

:A vaginal microbicide should prevent pathogen transmission without disrupting tissue barriers to infection. Ideally, it would not need to be applied immediately before sexual intercourse, when compliance is a problem. Intravaginal administration of small interfering RNA (siRNA) lipoplexes targeting Herpes Simplex Virus Type 2 (HSV-2) genes protects mice from HSV-2. However, protection is short-lived, and the transfection lipid on its own unacceptably enhances transmission. Here, we show that cholesterol-conjugated (chol)-siRNAs without lipid silence gene expression in the vagina without causing inflammation or inducing interferons. A viral siRNA prevents transmission within a day of challenge, whereas an siRNA targeting the HSV-2 receptor nectin-1 protects for a week, but protection is delayed for a few days until the receptor is downmodulated. Combining siRNAs targeting a viral and host gene protects mice from HSV-2 for a week, irrespective of the time of challenge. Therefore, intravaginal siRNAs could provide sustained protection against viral transmission.

journal_name

Cell Host Microbe

journal_title

Cell host & microbe

authors

Wu Y,Navarro F,Lal A,Basar E,Pandey RK,Manoharan M,Feng Y,Lee SJ,Lieberman J,Palliser D

doi

10.1016/j.chom.2008.12.003

subject

Has Abstract

pub_date

2009-01-22 00:00:00

pages

84-94

issue

1

eissn

1931-3128

issn

1934-6069

pii

S1931-3128(08)00401-0

journal_volume

5

pub_type

杂志文章

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