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Credit: https://www.technologynetworks.com/genomics/blog/improving-gene-editing-by-promoting-error-free-repair-of-crisprcas9-cut-dna-335118

New gene-editing therapy shows potential in eliminating high-resistance cancers

March 10, 2021

  • A research team based in the University of Tel Aviv has developed a new cancer therapy that optimizes genome editing in order to destroy cancer cells
  • The new therapy will work by utilizing the LNP system; a technique that improves nucleic acid encapsulation, delivery, and release
  • If application of the new therapy proves successful, then it could inevitably eliminate high-resistance cancers and prevent remission

In the past 20 years alone, there has been a massive wave of groundbreaking technology that has no-doubt reshaped the field of medicine into what it is today. Some of these breakthroughs have spearheaded the creation and development of innovative treatments—from a genome standpoint—that specifically target debilitating diseases. This has not only transformed our perspective and approach towards the treatment and cure of chronic and debilitating diseases, but also brought forth the development of a much more advanced clinical method of analysis; making medical research more accurate and effective. In fact, the therapeutic abilities and results of gene-editing technology cannot be downplayed. So much so that the lead-scientists behind the development of CRISPR—Dr Emmanuelle Charpentier and Dr. Jennifer Doudna—were awarded the Nobel Peace Prize in Chemistry in 2020. Of particular interest is the approach that CRISPR has taken with cancer. As you know, cancer is primarily a genetic disease; which arises from different mutations in areas of the body that regulate and control a number of bodily functions responsible for growth, mobility, and survival. The accumulation of these dangerous mutations over time leads to target cells becoming cancerous. This is one of the main reasons why cancer treatment is so complex and difficult to treat; mainly because of all the mutations that spring forth and result in resistance over time. To make things worse, cancer drugs are consumed repeatedly over time; meaning resistance will make drugs unresponsive. On the bright side, CRISPR gene-editing primarily targets DNA; meaning it has the potential to permanently disrupt or even eliminate any tumor surviving genes; bringing much-needed hope and promise for cancer patients and survivors. However, challenges in creating a safe and efficient delivery system have currently slowed down the application of CRISPR. But all this could change as a new study conducted by Dr. Daniel Rosenblum—in conjunction with his team based at the University of Tel Aviv—has managed to develop a new cancer therapy that optimizes CRISPR-Cas9 genome editing; which then destroys cancer cells. If the new technique proves successful, it could permanently disrupt tumor-survival genes in much fewer doses than it would ideally take traditional chemotherapy; and further minimize the risk of cancer resistance and remission. One of the ways that this technique can be implemented is by focusing on vital pathways necessary for tumor growth such as EGF within tumor tissue. The new therapy will work by utilizing the non-viral lipid nanoparticle delivery system, also known as LNP; a technique that allows for efficient nucleic acid encapsulation, delivery, and overall release. Before this study, LNP was used exclusively for tinier sections of RNA. Therefore, the research team has to create a new type of LNP that is more suitable for DNA editing. This new LNP works by improving the amount of genomic material being delivered; thereby making it more stable, and less likely to trigger any kind of immune responses. In fact, during the study, the research team found that injecting CRISPR-LNP was found to inhibit the growth and development of tumors; especially in complex brain cancer glioblastoma models, as well as metastatic ovarian cancer. Moreover—in mice that exhibited glioblastoma—the inclusion of this therapy improved their chances of survival by up to 30% If you put into perspective the high levels of resistance that traditional chemotherapies exhibit both in the treatment of glioblastoma and high-grade ovarian cancer, then this new therapy is extremely promising. “This is the first study in the world to prove that the CRISPR genome-editing system can be used to treat cancer efficiently in a living animal,” says lead investigator on the study, Professor Dan Peer. You have to remember that this is not chemotherapy. There are no bearing and underlying side effects as the cancer cells are treated in a way that they will never become active again. As such, the molecular scissors of Cas9 should ideally cut the cancer cell’s DNA; thereby neutralizing it and permanently preventing replication. Once the study came to a close, researchers also noted that the LNP system for CRISPR-Cas9 gene editing showed that it was able to permanently disrupt the genome of 98% cancer cells in vitro, and 80% cancer cells in vivo. With such groundbreaking information delivered to the public, it raises hope that there might be an effective DNA-targeted cancer therapy right around the corner; one that will inevitably eliminate high-resistance cancers which have proven a headache in the medical fraternity.

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