In terms of genesis, clinical presentation, and prognosis, acute myeloid leukemia (AML) is a diverse hematological malignancy [1]. Clinical results in AML patients are typically subpar despite current treatment [2]. Myeloid or lymphoid progenitors in the bone marrow can develop into leukemia, which is a clonal cancer. AML emerged from somatic mutations in myeloid lineage precursors along with transcriptome dysregulation of bone marrow infiltration, which led to the production of immature myeloid cells (blasts) and interruption of regular hematopoiesis. AML is identified by high blast counts in the blood, where a presentation of 20% or more blasts is deemed to be AML[3].The susceptibility of AML sufferers to life-threatening infectious headaches is enormously stated as it's miles the important motive of morbidity and mortality on this group[4]. miRNAs are small non-coding RNAs (18–24 nucleotides) that perform post-transcriptional regulation of mRNAs, mainly playing an inhibiting role when binding to the mRNA 3 untranslated region, ultimately impeding their translation or leading to degradation[5]. miRNAs regulate several biological processes, including cellular differentiation, proliferation, and apoptosis; thus, they can be easily found in blood samples and are easy to obtain and minimally invasive[5] . miRNAs are also essential for cancer progression due to reported observations that they play critical roles in regulating cancer signaling mechanisms, enhancing several factors, including tumor growth, angiogenesis, and metastasis[6, 7]. Despite numerous discoveries in the CRISPR / Cas system, its application in diagnostics and gene therapy has only been developed in the last few decades. In 2012, it was reported that CRISPR nucleases can be programmed simply by changing the guide RNA (gRNA) sequence, which is extremely useful for genome editing[8]. In 2013, scientists succeeded in editing a variety of cell types using a specific type II Cas protein called Cas9[9]. In 2015, two CRISPR / Cas type V proteins, Cas12a and Cas13a, were discovered for genome editing and were originally named Cpf1 and C2c2, respectively[10-12]. Cas13a (known as C2c2), another novel RNA-guided system with the ability to target RNA, has recently been discovered[13]. After recognizing and binding to the target RNA, Cas13a will activate the capacity of collateral cleavage to the untarget RNAs. However, the collateral cleavage activity of this system was not identified in eukaryotic species and its underlying mechanism were poorly understood[14]. So far, this type of CRISPR-based RNA targeting tool has already been used in biomedical applications, such as the detection of specific sequences of patient viral RNA or tumor circulating RNA[15]. The RNA-targeting gene editing systems have great potential in the treatment of cancer and malignant diseases by manipulating critical RNA molecules (both mRNAs and non-coding RNAs such as microRNAs, lncRNAs, etc.)[16].
In this study, using bioinformatics software and targeting microRNA precursors involved in acute myeloid leukemia (AML) metastasis, a new method for post-transcriptional regulation of this cancer was proposed. Also, in order to increase the accuracy and specificity of the technique proposed in this study (CRISPR-C2c2), first the analyzes were performed at the design level of the target crRNA and then structural studies were performed using structural bioinformatics methods. The help of bioinformatics tools, especially the CRISPR-C2c2 system, can have a significant impact on reducing the cost, time and frequency of trial and error of researchers.