Expanding Horizons of CRISPR/Cas Technology: Clinical Advancements, Therapeutic Applications, and Challenges in Gene Therapy

Abstract

CRISPR-Cas technology has transformed the field of gene editing, opening new possibilities for treatment of various genetic disorders. Recent years have seen a surge in clinical trials using CRISPR-Cas-based therapies. This review examines the current landscape of CRISPR-Cas implementation in clinical trials, with data from key registries, including the Australian New Zealand Clinical Trials Registry, the Chinese Clinical Trial Register, and ClinicalTrials.gov. Emphasis is placed on the mechanism of action of tested therapies, the delivery method, and the most recent findings of each clinical trial.

Keywords: CRISPR–Cas; gene therapy; genome editing; xenotransplantation.

Figure 1

Milestones in the history of CRISPR–Cas technology from its discovery in 1987 until the first FDA-approved gene therapy using CRISPR–Cas9 for genome modification: Ishino [21], Jansen [22], Bolotin [23], Mojica [24], Pourcel [25], Barranougou [26], Deltcheva [27], Jinek [1], Cong [28], Shmakov [29], Cyranoski [30].

Figure 2

CTX001 mechanism of action. (A) BCL11A promotes βs-globin expression while suppressing γ-globin expression, resulting in HbS production and the formation of crescent-shaped cells. (B) Knockdown of BCL11A, achieved by introducing a cut at the binding region of transcription factors GATA1/TAL1, enables γ-globin gene expression, leading to HbF production and the development of healthy erythrocytes.