Nanocarriers can be used to control the activity of genome editing in a spatiotemporal way by using stimulusresponsive nanocarriers

CRISPR/Cas9 is a genome editing technology that uses an RNA-guided programmable nuclease, Cas9, for genomic engineering. Recently, viral delivery-based genome editing for the treatment of congenital blindness has proceeded into clinical trials. Despite advancements, the potential for immunogenicity and restricted viral nanoparticles have hampered therapeutic genome editing. In this context, stimuli-responsive nanoparticles that degrade or disassociate from genome editing machinery have a lot of promise. Phenylboronic acid (PBA) conjugated PEI and 2,3dimethylmaleic anhydride (DMMA) modified poly (ethylene glycol) bpolylysine (mPEG113bPLys100/DMMA), for example, is a pH responsive nanoparticle. PEI is a cationic polymer that has been widely employed for pH-responsive CRISPR/Cas9 delivery due to its high density of ionizable amines, which promotes the proton sponge effect for endosome escape. Injecting a plasmid carrying dead Cas9 into mice can upregulate the expression of miR524 for cancer treatment. Cas9 RNPs may be encased inside nanoscale ZIF8 via in situ self-assembly of 2 methylimidazole (2MIMs), zinc ions, and Cas9 RNP. Under acidic conditions, Zif8/Cas9 nanoparticles released 70% of Cas9 in only 10 minutes. The antigenic profile and content of cancer cell membranes are inherited from the source cells, resulting in homotypic targeting. In living cells, varying redox potential offers particular cues for spatiotemporal CRISPR/Cas9 delivery