Single-guide RNA (sgRNA) is an essential element of CRISPR-based genome editing therapies. While sgRNA itself is not a standalone drug, it plays a pivotal role in directing Cas proteins to specific genetic sequences for precise editing. Several sgRNA-based pipelines have entered clinical trials, primarily targeting genetic disorders and certain complex diseases. 

Key sgRNA-Based Clinical Pipelines 

     ●      CRISPR Therapeutics/Vertex Pharmaceuticals – Exa-Cel (Exagamglogene autotemcel) 

          ●      Target Diseases: Sickle cell disease (SCD) and transfusion-dependent beta-thalassemia (TDT). 

          ●      Mechanism: Uses sgRNA and Cas9 to disrupt the BCL11A gene in hematopoietic stem cells, reactivating fetal hemoglobin production. 

          ●      Clinical Status: In Phase III clinical trials, with promising results; regulatory filings for approval were submitted in 2023. 

     ●      Editas Medicine – EDIT-301 

          ●      Target Diseases: Sickle cell disease (SCD) and beta-thalassemia. 

          ●      Mechanism: Employs Cas12a (Cpf1) with sgRNA to precisely edit the HBG1/2 promoters, increasing fetal hemoglobin expression. 

          ●      Clinical Status: Phase I/II trials are ongoing, with early safety and efficacy data showing encouraging outcomes. 

     ●      Intellia Therapeutics – NTLA-2001 

          ●      Target Disease: Transthyretin amyloidosis (ATTR). 

          ●      Mechanism: In vivo delivery of sgRNA and Cas9 using lipid nanoparticles (LNPs) to disrupt the TTR gene, reducing toxic transthyretin protein levels. 

          ●      Clinical Status: Phase I trials have demonstrated significant reductions in serum TTR levels. 

     ●      Verve Therapeutics – VERVE-101 

          ●      Target Disease: Hypercholesterolemia. 

          ●      Mechanism: Uses base-editing technology guided by sgRNA to introduce specific edits into the PCSK9 gene, lowering LDL cholesterol levels. 

          ●      Clinical Status: Phase I trials are underway for patients with familial hypercholesterolemia. 

     ●      Caribou Biosciences – CB-010 

          ●      Target Disease: B-cell non-Hodgkin lymphoma. 

          ●      Mechanism: sgRNA-based editing to enhance allogeneic CAR-T cell therapy by removing immune-evasion genes. 

          ●     Clinical Status: Phase I trials are ongoing, with preliminary data showing durable responses. 

The sgRNA-driven clinical pipeline reflects the versatility and transformative potential of CRISPR-based therapeutics. From correcting monogenic disorders to treating complex conditions like cancer and cardiovascular diseases, these therapies are steadily progressing toward commercialization. Continued innovation in sgRNA design and delivery will further expand their therapeutic reach, offering hope for previously untreatable conditions.