Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair

CRISPR/Cas9-based therapeutics, especially those that can correct gene mutations via homology directed repair (HDR), have the potential to revolutionize the treatment of genetic diseases. However, HDR-based therapeutics are challenging to develop because they require simultaneous in vivo delivery of...

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Detalles Bibliográficos
Autores principales: Lee, Kunwoo, Conboy, Michael, Park, Hyo Min, Jiang, Fuguo, Kim, Hyun Jin, Dewitt, Mark A., Mackley, Vanessa A., Chang, Kevin, Rao, Anirudh, Skinner, Colin, Shobha, Tamanna, Mehdipour, Melod, Liu, Hui, Huang, Wen-chin, Lan, Freeman, Bray, Nicolas L., Li, Song, Corn, Jacob E., Kataoka, Kazunori, Doudna, Jennifer A., Conboy, Irina, Murthy, Niren
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2017
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968829/
https://www.ncbi.nlm.nih.gov/pubmed/29805845
http://dx.doi.org/10.1038/s41551-017-0137-2
Descripción
Sumario:CRISPR/Cas9-based therapeutics, especially those that can correct gene mutations via homology directed repair (HDR), have the potential to revolutionize the treatment of genetic diseases. However, HDR-based therapeutics are challenging to develop because they require simultaneous in vivo delivery of Cas9 protein, guide RNA and donor DNA. Here, we demonstrate that a delivery vehicle composed of gold nanoparticles conjugated to DNA and complexed with cationic endosomal disruptive polymers can deliver Cas9 ribonucleoprotein and donor DNA into a wide variety of cell types, and efficiently correct the DNA mutation that causes Duchenne muscular dystrophy in mice via local injection, with minimal off-target DNA damage.

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