An Antibody‐CRISPR/Cas Conjugate Platform for Target‐Specific Delivery and Gene Editing in Cancer
AbstractThe CRISPR/Cas system has been introduced as an innovative tool for therapy, however achieving specific delivery to the target has been a major challenge. Here, an antibody‐CRISPR/Cas conjugate platform that enables specific delivery and target gene editing in HER2‐positive cancer is introduced. The CRISPR/Cas system by replacing specific residues of Cas9 with an unnatural amino acid is engineered, that can be complexed with a nanocarrier and bioorthogonally functionalized with a monoclonal antibody targeting HER2. The resultant antibody‐conjugated CRISPR/Cas nanocomplexes can be specifically delivered and induce gene editing in HER2‐positive cancer cells in vitro. It is demonstrated that the in vivo delivery of the antibody‐CRISPR/Cas nanocomplexes can effectively disrupt the plk1 gene in HER2‐positive ovarian cancer, resulting in substantial suppression of tumor growth. The current study presents a useful therapeutic platform for antibody‐mediated delivery of CRISPR/Cas for the treatment of various cancers and genetic diseases.
