CRISPR gene editing successfully treats cancer in living animals

recent years, molecularly targeted inhibitors and immunotherapy have greatly improved cancer treatment, while also reducing toxicity and adverse reactions. However, most anti-cancer drugs now require repeated administration, which not only increases the toxicity and cost associated with treatment, but also seriously reduces the quality of life of patients. In addition, most types of cancer have high recurrence rates and resistance, so new treatments are urgently needed.CRISPR-Cas9 gene editing has the potential to permanently destroy tumor survival genes, overcoming repeated dose limits in traditional cancer therapies and improving treatment effectiveness. However, Cas9 and sgRNA are large, have some obstacles to conventional and non-viral delivery systems, and currently have relatively low gene editing rates due to delivery systems for non-liver tissue and tumors. Therefore, a new delivery system with substantially higher editorial efficiency is needed to improve the effectiveness of cancer treatment.Recently, researchers from Tel Aviv University in Israel published a study entitled CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancerrapy, which developed a new lipid-based nanoparticle delivery system that can be used for CRISPR-Cas9 genome editing with an efficiency of more than 84% and significantly inhibit tumor growth and improve survival by 80%. This innovation opens up new avenues for cancer treatment and research, and provides potential applications for targeted gene editing in non-cancerous tissues.Lipid nanoparticles (LNP) are clinically recognized non-viral nucleic acid transmission systems. The researchers used Cas9 mRNA instead of proton DNA and modified it and sgRNA to enhance RNA stability and reduce immunogenicity, while designing four ionized cation lipid co-packages Cas9mRNA and sgRNA from a new ionized amino lipid library. The biophysical properties of L8-cLNPs (CRISPR LNP) are similar to those of clinically approved LNP preparation MC3-cLNPs, and Cas9 mRNA and sgRNA have higher encapsulation efficiency. The efficiency and specificity of L8-cLNP destructive genes were evaluated, and it was found that the gene modification rate was up to 94%, and the editing rate on non-targeted gene constellations was less than 0.1%.PLK1 is a kinase needed for silk division, and lack of it can cause the G2-M cell cycle to stagnate and the dividing cells to die. To explore the potential of cLNPs for genome editing in cancer, the researchers used sgPLK1-cLNPs to treat cancer cell lineages for two invasive and difficult-to-treat cancers: glioblastoma and metastatic ovarian cancer. It was found that the gene editing can effectively destroy the PPK1 gene, the editing rate in both cancer cells can reach 84% and 91%, after 48 hours of treatment of both cancer cell line has cell cycle stagnation and death, and after treatment-related dose systemic dosing experiments to ensure that L8-cLNPs are not toxic or immunogenic.The researchers then assessed the therapeutic efficacy of cLNPs in the body. The sgPLK1-cLNPs stereotactic injection was injected into the built tumor mouse model to analyze the PPK1 gene editing efficiency in single-cell tumor suspension and the apoptosis and tumor growth inhibition caused by PLC1 gene damage. About 68% of tumor cells in the PPK1 gene base were edited, and PLC1-dependent apoptosis occurred, and a single intra-tumor injection sgPLK1-cLNPs significantly inhibited tumor growth, increasing the mice's medium survival from 32.5 days to more than 48 days, and the survival rate increased by 30%.Most tumors, including metastasis or blood tumors, require systemic medication, but most LNP is trapped in the liver and other central organs and cannot be effectively absorbed by tumor cells. The researchers tested the efficacy of sgPLK1-cLNPs targeting EGFR in metastatic ovarian adenocarcinoma models and found that it effectively inhibited tumor growth and improved overall survival, with about 82% of tumor cells in the PPK1 gene base edited and mice increasing their total survival by about 80%. This also shows that targeted cLNPs can be used to target the treatment of diffuse tumors.Dan Peer, co-author of the study, said: "This is the first study in the world to demonstrate that CRISPR genome editing systems can be used to effectively treat cancer in living animals. And it's not chemotherapy, there are no side effects, and cancer cells treated in this way will never be active again. The technology also opens up many new possibilities for treating other types of cancer, as well as chronic viral diseases such as rare genetic diseases and AIDS. "(Biological Exploration):.CRISPR-Cas9 genome editing using targeted lipid nanoparticles for cancer therapy