CRISPR Cas systems: From bacterial defense mechanisms to revolutionary tools reshaping genetic research and translation therapeutics

The CRISPR-Cas systems, initially identified as bacterial defense mechanisms, have become innovative tools for genetic research and translational therapeutics. These systems are made up of clustered regularly interspaced short palindromic repeats (CRISPR) and CRISPR-associated (Cas) proteins, which precisely target and cleave specific genome sequences, thus providing bacteria with immunity against viral infections. This review traces the evolution of CRISPR-Cas systems from their discovery as a bacterial defence mechanism to present uses in genetic engineering and beyond. The diversity of these systems, their structure and function, and the profound impact of these systems on genetic research, including their use in the creation of novel therapies for a variety of diseases, will be explored. In particular, this review discuss therapeutic applications of CRISPR in various neurodegenerative disorders (Alzheimer disease, Huntington’s disease and Parkinson’s disease), cardiovascular diseases, viral disorders including HIV, blood disorders (β-thalassemia, haemophilia and sickle cell anaemia), ocular disorders (Retinitis pigmentosa, Leber's congenital amaurosis, Aniridia, X-linked juvenile retinoschisis) mitochondrial disorders, Duchene muscular dystrophy and cancer along with the prospects concerning them. Furthermore, we discuss recent advancements, including novel Cas variants (CasΦ, CasX/Cas12f), precision editing technologies (base editing and prime editing), advanced delivery systems (nanoparticles, viral vectors), and emerging diagnostic platforms (SHERLOCK and DETECTR). Despite the extensive literature available on CRISPR-Cas systems, there remains a need for an updated review addressing recent developments, technological advancements, and future directions. This review aims to fill this gap by presenting an in-depth analysis of cutting-edge research, distinguishing itself from previous reviews by incorporating newly discovered CRISPR-Cas variants, emerging therapeutic strategies, and evolving regulatory landscapes.