Effective Genome Editing Using CRISPR-Cas9 Nanoflowers.
Chen ZhangHe RenGengqi LiuJiexin LiXiaojie WangYumiao ZhangPublished in: Advanced healthcare materials (2022)
CRISPR-Cas9 as a powerful gene-editing tool has tremendous potential for the treatment of genetic diseases. Herein, a new mesoporous nanoflower (NF)-like delivery nanoplatform termed Cas9-NF is reported by crosslinking Cas9 and polymeric micelles that enables efficient intracellular delivery and controlled release of Cas9 in response to reductive microenvironment in tumor cells. The flower morphology is flexibly tunable by the protein concentration and different types of crosslinkers. Cas9 protein, embedded between polymeric micelles and protected by Cas9-NF, remains stable even under extreme pH conditions. Responsive cleavage of crosslinkers in tumor cells, leads to the traceless release of Cas9 for efficient gene knockout in nucleus. This crosslinked nanoparticle exhibits excellent capability of downregulating oncogene expression and inhibiting tumor growth in a murine tumor model. Taken together, these findings pave a new pathway toward the application of the protein-micelle crosslinked nanoflower for protein delivery, which warrants further investigations for gene regulation and cancer treatment.
Keyphrases
- crispr cas
- genome editing
- cancer therapy
- drug delivery
- signaling pathway
- drug release
- protein protein
- lps induced
- binding protein
- amino acid
- oxidative stress
- copy number
- nuclear factor
- genome wide
- hyaluronic acid
- poor prognosis
- pi k akt
- cell proliferation
- photodynamic therapy
- gene expression
- small molecule
- dna methylation
- climate change
- genome wide analysis