Here, we describe a protocol to prepare and administer glucan-encapsulated RNAi particles (GeRPs), for specific delivery of siRNA and subsequent gene silencing in Kupffer cells (KCs) in mice. This technology is based on baker's yeast and allows gene manipulation in macrophages in a tissue-specific manner depending on the route of administration and the model that is used. GeRP administered by intravenous injection in mice are delivered to KCs. Therefore, using the GeRP technology to silence genes provides a unique method to study the function of factors expressed by KCs in the regulation of liver function.

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