February 1, 2024
A Breakthrough in Cancer Treatment: Nanotechnology-Based CRISPR/Cas9 Delivery System
Scientists are making significant strides in the field of cancer treatment with the development of a nanotechnology-based CRISPR/Cas9 delivery system. This groundbreaking approach, detailed in a recent study published in MedComm—Biomaterials and Applications by Professor Changyang Gong and Ph.D. student Shiyao Zhou, holds immense promise for targeted genome editing in cancer therapy.
The CRISPR/Cas9 system, comprising the Cas9 protein and single-stranded directing RNA (sgRNA), operates by precisely guiding the Cas9 endonuclease to target regions with the presence of protospacer adjacent motif (PAM). This results in DNA double-strand breaks (DSBs), leading to site-specific genomic changes. The subsequent DNA repair occurs through nonhomologous end joining (NHEJ) or homology-directed repair (HDR) pathways.
Building upon the inherent capabilities of the CRISPR/Cas9 system, scientists have expanded its utility to include gene targeting activation and inhibition tools known as CRISPRa and CRISPRi, respectively, based on dCas9.
The study outlines three forms of CRISPR/Cas9 cargos: plasmids, mRNA/sgRNA, and ribonucleoprotein (RNP) complexes, each with its distinct advantages and limitations. However, the challenge lies in effectively delivering CRISPR/Cas9 into target cells, necessitating the development of a robust nanotechnology strategy for delivery.
The paper summarizes nanotechnology-based delivery techniques for the treatment of cancer across the three cargo categories. While viral vectors have traditionally been used for CRISPR/Cas9 delivery, their applications are restricted due to limitations such as limited packaging capacity, high immunogenicity, and lack of tissue targeting.
Addressing these limitations, nanocarriers, including cationic lipid-based nanoparticles, cationic polymer/polypeptide-based nanoparticles,
