Macrophages are key components of the host immune system with crucial roles in the response to and treatment of disease. Targeted modification of the macrophage genome using CRISPR/Cas9 technology could provide a powerful technique for the treatment of diseases through transient immune modulation. However, there are significant physiological, cellular, and intracellular barriers to effective delivery of the CRISPR machinery that have restricted <i>in vivo </i>Cas9 protein-based approaches to local/topical delivery applications. We utilized our gold nanoparticle (AuNP)-based self-assembled delivery platform for systemic (tail-vein) administration of the CRISPR/Cas9 machinery. We observed highly selective delivery to macrophage cells of the liver and spleen, with concurrent gene editing efficiency of &gt;8%, and no observed negative immunological effects.

<i>In vivo </i>editing of macrophages through systemic delivery of CRISPR/Cas9 RNP-nanoparticle nanoassemblies

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

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In vivo editing of macrophages through systemic delivery of CRISPR/Cas9 RNP-nanoparticle nanoassemblies