한빛사논문
Seungju Yang 1, San Hae Im 1, Ju Yeon Chung 1, Juhee Lee 1, Kyung-Hun Lee 2 3, Yoo Kyung Kang 4 and Hyun Jung Chung 1 *
1Department of Biological SciencesKorea Advanced Institute of Science and TechnologyDaejeon 34141, Republic of Korea
2Department of Internal Medicine Seoul National University Hospital Seoul 03080, Republic of Korea
3Cancer Research Institute Seoul National University Seoul 03080, Republic of Korea
4College of Pharmacy Gyeongsang National University Jinju 52828, Republic of Korea
*Corresponding author: correspondence to Hyun Jung Chung
Abstract
The 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.
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