CRISPR/Cas9 based therapeutics have the potential to revolutionize the treatment of genetic diseases. However, developing Cas9 based therapeutics that can correct gene mutations requires simultaneously delivering Cas9, guide RNA (gRNA), and donor DNA in vivo, and safe and effective methods for delivering these three classes of biomolecules simultaneously have not been developed. In this report, we present a delivery vehicle termed CRISPR-Gold, which can deliver Cas9 protein, gRNA, and donor DNA in vivo and correct gene mutations via homology directed DNA repair (HDR). CRISPR-Gold is composed of gold nanoparticles assembled with the Cas9/gRNA ribonucleoprotein (RNP) complex, donor DNA, and an endosomal disruptive polymer. We show here that CRISPR-Gold can correct the DNA mutation that causes Duchenne muscular dystrophy (DMD) in mice via HDR. CRISPR-Gold is the first example of a non-viral delivery vehicle that can generate HDR in vivo with the Cas9 protein and holds great promise for treating genetic diseases.

Genome editing in vivo with the delivery of Cas9 ribonucleoprotein and donor DNA complexed to nanoparticles

253rd National Meeting (2017)

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