Current Status of CRISPR/Cas9 Application in Clinical Cancer Research: Opportunities and Challenges

Abstract

Cancer is considered by not only multiple genetic but also epigenetic amendments that drive malignant cell propagation and consult chemo-resistance. The ability to correct or ablate such mutations holds enormous promise for battling cancer. Recently, because of its great efficiency and feasibility, the CRISPR-Cas9 advanced genome editing technique has been extensively considered for therapeutic investigations of cancers. Several studies have used the CRISPR-Cas9 technique for editing cancer cell genomic DNA in cells and animal cancer models and have shown therapeutic potential in intensifying anti-cancer protocols. Moreover, CRISPR-Cas9 may be used to correct oncogenic mutations, discover anticancer drugs, and engineer immune cells and oncolytic viruses for immunotherapeutic treatment of cancer. We herein discuss the challenges and opportunities for translating therapeutic methods with CRISPR-Cas9 for clinical use and suggest potential directions of the CRISPR-Cas9 system for future cancer therapy.

CRISPR/Cas9 ribonucleoprotein (RNP) complex enables higher viability of transfected cells in genome editing of acute myeloid cells

“…Gene editing, especially CRISPR/Cas9-mediated gene editing, has paved the way for new approaches to cancer therapy. Nanoparticle delivery of CRIPR/Cas9 has been used to rescue fragile X syndrome in mouse model (8), and lentivirus-delivered CRIPR/Cas9 has been confirmed the positive therapeutic role on malignancy (23)(24)(25)(26). However, due to the off-target effects of CRISPR/ Cas9 and the delivery vehicle, its application has been limited.…”

Application Perspectives of Nanomedicine in Cancer Treatment

“…Wang et al constructed a DNA nanodevice using DNA origami technology to co-deliver siRNA and the doxorubicin (Nanodevice-siBcl2-si P-glycoprotein-doxorubicin), which induced potent cytotoxicity and tumor growth inhibition with no observable systemic toxicity (Wang X. et al, 2021). CRISPR/Cas9 gene editing technology, another cancer genesuppression therapy, has the potential to permanently destroy tumor survival genes, which overcomes the repeated dosing limitations of traditional cancer therapy and improves the therapeutic effect (Rafii et al, 2022). CRISPR/Cas9 consists of two parts: Cas9, a nuclease that cuts DNA at a target site, and a single guide RNA (sgRNA) that directs Cas9 to cut at a specific or desired site in DNA.…”

“…CRISPR/Cas9 gene editing technology, another cancer gene-suppression therapy, has the potential to permanently destroy tumor survival genes, which overcomes the repeated dosing limitations of traditional cancer therapy and improves the therapeutic effect ( Rafii et al, 2022 ). CRISPR/Cas9 consists of two parts: Cas9, a nuclease that cuts DNA at a target site, and a single guide RNA (sgRNA) that directs Cas9 to cut at a specific or desired site in DNA.…”

Understanding on CRISPR/Cas9 mediated cutting-edge approaches for cancer therapeutics

“…The CRISPR technology holds the potential to permanently disrupt the genes required for tumour cell survival thereby ablating the need of repeated chemotherapy administration, which ultimately may improve treatment efficacy while requiring less treatment visits, reducing the cost. However, achieving an effective treatment will require a significantly high gene editing efficiency to get the therapeutic benefit [ 72 , 73 ]. A recent study by Rosenblum et al reports that CRISPR-Lipid nanoparticles (cLNPs), when targeted against PLK1 (sgPLK1-cLNP) in fast-growing glioblastoma, was able to achieve ~ 70% in-vivo gene editing (using single intraperitoneal inoculation) leading to cellular apoptosis in the tumour, which, in turn, caused up-to ~ 50% reduction in tumour progression while increasing the survival rate by 30% at the same time.…”