KAIST 정현정 교수 연구팀은 크리스퍼 단백질에 특정 아미노산을 변경시켜 다양한 생체분자를 더 많이 결합시키는 방법으로 생체 내 본질적인 생화학 과정을 방해하지 않는 단백질인 크리스퍼 나노복합체(⍺Her-CrNC, anti-Her2 conjugated CRISPR nanocomplex)를 개발했다.

연구진은 이 크리스퍼 나노복합체가 난소암 세포나 동물모델 암세포의 종양 항원에 전달되는 걸 확인했다. 

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. 

Adv Sci_2024.03.29.

https://onlinelibrary.wiley.com/doi/10.1002/advs.202308763