مقالات پذیرفته شده در ششمین کنگره بین المللی زیست پزشکی
The role of the CRISPR technique in the treatment of Acute lymphoblastic leukemia
The role of the CRISPR technique in the treatment of Acute lymphoblastic leukemia
sahar eskandari,1,*
1. 1.Msc of Molecular Genetic Department of Genetics, Zanjan Branch, Islamic Azad University, Zanjan, Iran.
Introduction: Introduction and aim: Acute lymphoblastic leukemia (ALL) is a cancerous condition that develops from hematological B- or T-cell progenitors and is characterized by significant genetic and clinical variability. Powerful animal genetic models that simulate cooperative oncogenic lesions affecting genes with a known involvement in the proliferation and establishment of the leukemic clone have been created thanks to the advent of novel tools for genetic editing like CRISPR-Cas9. The CRISPR-Cas9 technique is based on the Cas9 nuclease producing a guided cut in the double strand of DNA. This technology has the potential for multiplex genome editing. One 20-nucleotide RNA strand, which precisely pinpoints the breakage location, is responsible for this. After DNA cutting, the repair machinery of the host cell leads to repair errors and thereby promotes a modification of the original sequence by a mutation such as an insertion, deletion, or in-version, among others. the aim of this study was to the role of the CRISPR technique in the treatment of leukemia.
Methods: Search Method: The current study was carried out by searching scholarly databases such as Google Scholar, Science Direct, Springer, and PubMed for investigating CRISPR in leukemia.
Results: Results: Results revealed that genome editing techniques have advanced and are now used in therapeutic and clinical settings. Their use has made it easier to create novel treatments like chimeric antigen receptors (CARs) and has made it possible to investigate the genes implicated in the development of pathogenesis. The foundation of the genome editing system is the employment of designed nucleases that have non-specific DNA cleavage modules coupled to sequence-specific DNA-binding domains. These chimeric nucleases cause DNA double-strand breaks (DSBs), which activate cellular DNA processes such as homologous recombination and error-prone non-homologous end joining (NHEJ) (HR). CRISPR interference (CRISPRi) and CRISPR activation (CRISPRa) developed from the CRISPR-Cas9 system. CRISPRi uses a catalytically inactive version of Cas9 (dCas9) lacking endonucleolytic activity in combination with a sgRNA designed with a 20-bp complementary region to any gene of interest to silence a target gene. While CRISPRa uses fusions of dCas9 to activator domains to activate gene expression.
Conclusion: Conclusions: Future efforts to create mouse leukemia models that mirror human malignancies may benefit from the development of genomic editing techniques. In this regard, the disease's multigenic basis presents significant challenges. Murine models of ALL based on a single change have been unable to fully develop the disease, at least in part. We might approach the true clinical settings and create a more effective model for the study of this type of tumor by combining several of the gene changes discovered in patients in a mouse model. Creating an animal model with many genetic modifications used to be a time-consuming and expensive operation, but techniques like CRISPR-Cas9 now make it possible to introduce multiple mutations at once. Thus, it will be possible to produce more complicated animal models in a shorter amount of time, enabling us to more accurately mimic the conditions that exist in patients and providing the necessary framework for researching and creating novel therapeutic approaches. In addition, genome editing tools in the clinic will support the advancement of customized medicine by tying together genomes, disease phenotypes, and treatment objectives. By utilizing these technologies, we will be able to identify novel mechanisms of acquired resistance to pathway target treatments and expand our understanding of the mode of action of these innovative medications. The safety and effectiveness of medicines must be addressed before genome editing technologies can be applied in a clinical context. One of the biggest barriers to this technology is still the off-target effect. In the future, researchers will need to develop better genetic tools to get rid of any off-target effects and boost the effectiveness of gene editing. Despite this, genome editing presents fresh possibilities for treating conditions like ALL that were beyond the scope of earlier treatments.
Keywords: CRISPR technique, Acute lymphoblastic leukemia, cancer