β-Thalassemia gene editing therapy: Advancements and difficulties

Medicine (Baltimore). 2024 May 3;103(18):e38036. doi: 10.1097/MD.0000000000038036.

Abstract

β-Thalassemia is the world's number 1 single-gene genetic disorder and is characterized by suppressed or impaired production of β-pearl protein chains. This results in intramedullary destruction and premature lysis of red blood cells in peripheral blood. Among them, patients with transfusion-dependent β-thalassemia face the problem of long-term transfusion and iron chelation therapy, which leads to clinical complications and great economic stress. As gene editing technology improves, we are seeing the dawn of a cure for the disease, with its reduction of ineffective erythropoiesis and effective prolongation of survival in critically ill patients. Here, we provide an overview of β-thalassemia distribution and pathophysiology. In addition, we focus on gene therapy and gene editing advances. Nucleic acid endonuclease tools currently available for gene editing fall into 3 categories: zinc finger nucleases, transcription activator-like effector nucleases, and regularly interspaced short palindromic repeats (CRISPR-Cas9) nucleases. This paper reviews the exploratory applications and exploration of emerging therapeutic tools based on 3 classes of nucleic acid endonucleases in the treatment of β-thalassemia diseases.

Publication types

  • Review

MeSH terms

  • CRISPR-Cas Systems
  • Gene Editing* / methods
  • Genetic Therapy* / methods
  • Humans
  • Transcription Activator-Like Effector Nucleases / genetics
  • Zinc Finger Nucleases / genetics
  • beta-Thalassemia* / genetics
  • beta-Thalassemia* / therapy

Substances

  • Transcription Activator-Like Effector Nucleases
  • Zinc Finger Nucleases