Application of CRISPR/Cas9 based therapy in SCD, DMD and HIV

Gene editing has revolutionised the possibilities of molecular biology, and the emergence of CRISPR as the novel groundbreaking genome engineering tool has since proved superior to its predecessors such as TALENs and ZFNs owing to its cost-effectiveness, simplicity of design, flexibility and high specificity. Under the guidance of gRNA, the endonuclease Cas9 could achieve manipulation at nearly any location. This review concentrates on the application of CRISPR/Cas9 based therapies in three diseases-SCD, DMD and HIV. By taking a corresponding drug or frontier research as an example, its mechanism and efficiency are clearly illustrated. For instance, Casgevy, a CRISPR/Cas9 based drug, used to treat SCD, which could modify the mutation in HBB and rescue the aberrant production of foetal haemoglobin, has proven to be in high efficiency. In the therapy of DMD, a similar strategy is adopted, except taking AAV as the delivery vector. For HIV treatment regimen, instead of targeting host genome, the Cas9 aims to engineer the promoter of pathogen, inhibiting the pathogen activity and clearing the latent infected HIV virus permanently. According to the clinical data, all of these methods tend to be therapeutic alternatives. However, despite CRISPR/Cas9s plethora of merits, its challenges require further in-depth research and strategies of prevention before its routine application in disease treatment. This review briefly discusses its most significant shortcoming of off-targets effects, which can lead to fatal genetic mutations, and the potential interventions.