Nanotechnology-based delivery of CRISPR/Cas9 for cancer treatment

Xiaoyu Xu; Chang Liu; Yonghui Wang; Oliver Koivisto; Junnian Zhou; Yilai Shu; Hongbo Zhang

doi:10.1016/j.addr.2021.113891

Nanotechnology-based delivery of CRISPR/Cas9 for cancer treatment

Adv Drug Deliv Rev. 2021 Sep:176:113891. doi: 10.1016/j.addr.2021.113891. Epub 2021 Jul 26.

Authors

Xiaoyu Xu¹, Chang Liu², Yonghui Wang², Oliver Koivisto², Junnian Zhou³, Yilai Shu⁴, Hongbo Zhang⁵

Affiliations

¹ ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200031, China; Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland.
² Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland.
³ Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland; Experimental Hematology and Biochemistry Lab, Beijing Institute of Radiation Medicine, Beijing 100850, China; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku 20520, Finland.
⁴ ENT Institute and Department of Otorhinolaryngology, Eye & ENT Hospital, State Key Laboratory of Medical Neurobiology, Institutes of Biomedical Sciences, Fudan University, Shanghai 200031, China.
⁵ Pharmaceutical Sciences Laboratory, Faculty of Science and Engineering, Åbo Akademi University, Turku 20520, Finland; Turku Bioscience Centre, University of Turku and Åbo Akademi University, Turku 20520, Finland. Electronic address: hongbo.zhang@abo.fi.

PMID: 34324887
DOI: 10.1016/j.addr.2021.113891

Abstract

CRISPR/Cas9 (Clustered Regularly Interspaced Short Palindromic Repeats-associated protein 9) is a potent technology for gene-editing. Owing to its high specificity and efficiency, CRISPR/Cas9 is extensity used for human diseases treatment, especially for cancer, which involves multiple genetic alterations. Different concepts of cancer treatment by CRISPR/Cas9 are established. However, significant challenges remain for its clinical applications. The greatest challenge for CRISPR/Cas9 therapy is how to safely and efficiently deliver it to target sites in vivo. Nanotechnology has greatly contributed to cancer drug delivery. Here, we present the action mechanisms of CRISPR/Cas9, its application in cancer therapy and especially focus on the nanotechnology-based delivery of CRISPR/Cas9 for cancer gene editing and immunotherapy to pave the way for its clinical translation. We detail the difficult barriers for CRISIR/Cas9 delivery in vivo and discuss the relative solutions for encapsulation, target delivery, controlled release, cellular internalization, and endosomal escape.

Keywords: CRISPR/Cas9; Cancer treatment; Clinic application; Delivery vectors; Gene editing; Nanotechnology.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
CRISPR-Cas Systems*
Gene Editing
Humans
Nanotechnology / methods*
Neoplasms / genetics
Neoplasms / therapy*