The Recent Advances in the Use of Molecular Scissors (Gene Editing Tool) for the Treatment of Diseases

Abstract

Sequencing of the human genome marked an important milestone in studying the genetic basis of disease states. Gene editing is a type of genetic engineering in which DNA is inserted, deleted, modified or replaced in the genome of a living organism. This review seeks to shed more light on the recent advances in the use of molecular scissors (gene editing tool) for the treatment of diseases. Molecular scissors, also known as restriction enzymes or endonucleases, are a class of enzymes that play a crucial role in genetic engineering. Several nucleases genome editing strategies, including Zinc Finger Nucleases (ZFNs), Transcription Activator-like Effector Nucleases (TALENs), and Clustered Regularly Interspaced Short Palindromic Repeats-CRISPR associated proteins (CRISPR-Cas), are the most widely used gene editing techniques. The basic mechanism involved in genetic manipulations is the recognition of target genomic loci and binding of effector DNA-binding domain (DBD), double-strand breaks (DSBs) in target DNA by the restriction endonucleases (FokI and Cas), and the repair of DSBs through homology-directed recombination (HDR) or non-homologous end joining (NHEJ). With the continuous optimizations of these technologies, ZFNs, TALENs, and CRISPR-Cas9 have already entered human clinical trials. To date, the majority of clinical applications of these technologies are focused on ex vivo gene editing therapeutics, which are highly effective for many medical conditions, although with known limitations, the in vivo applications of CRISPR technologies are also challenged with issues. Moreover, the novel innovations, such as Base editing and Prime editing, are still at the pre-clinical stage.