Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair
- 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
- et al.
Published Web Location
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5968829/Abstract
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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