CRISPR-Cas9-mediated therapeutics: Current clinical trials and therapy approval landscape to treat human diseases

The genome editing technology using CRISPR-Cas9 has created a new trajectory for treating diverse human diseases. The approval of CRISPR-Cas9 therapeutics was first given to Casgevy for treating transfusion-dependent β-thalassemia (TDT) by the UK Medicines and Healthcare Products Regulatory Agency (UKMHRA) on November 16, 2023. Subsequently, UKMHRA approved Casgevy for the treatment of sickle cell disease (SCD), which was approved by the US Food and Drug Administration (FDA) on December 8, 2023. The approval has created a new era of gene editing medicine. Numerous clinical trials have been initiated to treat different human diseases. In this comprehensive review, we present an overview of the therapeutic development that includes the earliest days of research using CRISPR-Cas9 technology, clinical trials, UKMHRA/FDA-approved therapeutics (Casgevy), and the CRISPR-Cas9 technology approved for the therapy of SCD and TDT. We also present details on the role of biopharmaceutical industry-academia collaboration and patent landscape of the CRISPR-Cas9 technology. Finally, the therapeutics' challenges, safety concerns, and cost-effectiveness are illustrated to provide a complete understanding on the current landscape of CRISPR-Cas9-mediated therapeutics for countries' policymakers, biopharmaceutical companies, and next-generation researchers to formulate the future strategies.