CRISPR/Cas9 based therapeutics have the potential to revolutionize the treatment of genetic diseases. One particularly exciting class of Cas9 therapeutics are therapies that can correct gene mutations via homology directed repair (HDR).
However, HDR based therapeutics have been challenging to develop because they require simultaneous delivery of Cas9 protein, guide RNA (gRNA), and donor DNA in vivo.
Our collaborative work determined that a delivery vehicle composed of gold nanoparticles conjugated to DNA and complexed with cationic endosomal disruptive polymers (termed CRISPR-Gold) can deliver Cas9 ribonucleoprotein (RNP) and donor DNA in vivo and correct gene mutations via HDR in number of mouse and human cells and in vivo, in DMD-MDX disease model. This work has lead to new biotech “Genedit” and our current focus is on novel design of CRISPR machinery that makes gene editing a therapeutic reality.
- Lee, MJ Conboy, et al, and I. Conboy and N. Murthy. 2017, in press Nature Biomedical Engineering. Nanoparticle delivery of Cas9 ribonucleoprotein and donor DNA in vivo induces homologous directed DNA repair.