Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homology-directed DNA repair
By Kunwoo Lee, M. Conboy, Hyo Min Park, F. Jiang, Hyun Jin Kim, M. DeWitt, Vanessa A Mackley, K. Chang, Anirudh Rao, Colin M. Skinner and 12 more. Nature Biomedical Engineering, 2017
659 citations recorded by the source corpus.
Clustered regularly interspaced short palindromic repeats (CRISPR)–CRISPR associated protein 9 (Cas9)-based therapeutics, especially those that can correct gene mutations via homology-directed repair, have the potential to revolutionize the treatment of genetic diseases. However, it is challenging to develop homology-directed repair-based therapeutics because they require the 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.Gold nanoparticles carrying Cas9 ribonucleoprotein and donor DNA, and complexed with endosomal disruptive polymers, correct the DNA mutation that causes Duchenne muscular dystrophy in mice, with minimal off-target effects.
Subfields: Molecular Biology
View Paper: https://www.semanticscholar.org/paper/93098303f320872196ce5ba06582f22e0416f3a8
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Citations in the corpus
- Delivering CRISPR: a review of the challenges and approaches (2018, background): “Lee et al. (2017) also reported use of AuNPs to deliver Cas9:sgRNA RNP to mice suffering from DMD.”
- Applications of genome editing technology in the targeted therapy of human diseases: mechanisms, advances and prospects (2020, background): “Furthermore, nonviral polymers conjugated to the gold nanoparticle hybridization system have been recognized as a suitable vehicle for the delivery of Cas9 RNP complexes plus donor DNA, which could effectively correct the disease phenotypes of muscle cells after intramuscular injection.(341)”
- CRISPR technology: A decade of genome editing is only the beginning (2023, background): “Compared with viral-based delivery, synthetic material–based delivery methods, which include LNPs (176), cationic polymers and peptides (177–181), and gold nanoparticles (182), are often safer and offer high levels of control and flexibility because they can be more easily tailored to all three form”
- Engineering the Delivery System for CRISPR-based Genome Editing (2018, background): “A recent study showed that gold nanoparticle-mediated Cas9 RNP delivery was successfully able to initiate both gene editing and HDR in vivo, one of the first demonstrated instances of successful non-viral mediated HDR [25].”