Abstract
Hematological malignancies (HM) are a group of neoplastic diseases that are usually heterogenous in nature due to the complex underlying genetic aberrations in which collaborating mutations enable cells to evade checkpoints that normally safeguard it against DNA damage and other disruptions of healthy cell growth. Research regarding chromosomal structural rearrangements and alterations, gene mutations, and functionality are currently being carried out to understand the genomics of these abnormalities. It is also becoming more evident that cross talk between the functional changes in transcription and proteins gives the characteristics of the disease although specific mutations may induce unique phenotypes. Functional genomics is vital in this aspect as it measures the complete genetic change in cancerous cells and seeks to integrate the dynamic changes in these networks to elucidate various cancer phenotypes. The advent of CRISPR technology has indeed provided a superfluity of benefits to mankind, as this versatile technology enables DNA editing in the genome. The CRISPR-Cas9 system is a precise genome editing tool, and it has revolutionized methodologies in the field of hematology. Currently, there are various CRISPR systems that are used to perform robust site-specific gene editing to study HM. Furthermore, experimental approaches that are based on CRISPR technology have created promising tools for developing effective hematological therapeutics. Therefore, this review will focus on diverse applications of CRISPR-based gene-editing tools in HM and its potential future trajectory. Collectively, this review will demonstrate the key roles of different CRISPR systems that are being used in HM, and the literature will be a representation of a critical step toward further understanding the biology of HM and the development of potential therapeutic approaches.
Highlights
Hematological malignancies (HM) are cancers that begin in the cells of blood-forming tissues such as the bone marrow or generally in the cells immune system
This review has clearly demonstrated that clustered regularly interspaced short palindromic repeats (CRISPR) has served well in deciphering and understanding the genetic basis of hematological malignancies and has bloomed to become the new gamechanger in the field of genome editing by overcoming all the limitations that were displayed by other editing techniques earlier
In spite of all the merits posed by this so-called prime technique, CRISPR come with certain limitations like its earlier predecessors
Summary
Hematological malignancies (HM) are cancers that begin in the cells of blood-forming tissues such as the bone marrow or generally in the cells immune system. Following pioneering studies on zinc-finger proteins, multiple effector domains have become accessible to support the fusion of TALE repeats for different genomic modification purposes, including nucleases, transcriptional activators, and site-specific recombinases. Their simpler cipher codes provide better simplicity in design than triplet-confined zinc-finger proteins, one of the primary technical hurdles for cloning repeat TALE arrays is the design of identical repeat sequences on a large scale. CRISPRainbow is a system for labeling DNA in human cells based on nuclease-dead (d) Cas combined with engineered single guide RNA (sgRNA) scaffolds that bind to fluorescent proteins In this applied science technique, it allows simultaneous imaging of up to seven chromosomal loci in an individual human cell and observes large differences in the chromodynamic properties of different chromosomal loci at a time. This system is a valuable tool for studying the transfiguration of the genome in real time basis, and it is used to label the DNA and track the movement of DNA in live cells (Ma et al, 2016)
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