Beyond current treatment of Fanconi Anemia: What do advances in cell and gene-based approaches offer?

Blood Rev. 2023 Jul:60:101094. doi: 10.1016/j.blre.2023.101094. Epub 2023 Apr 28.

Abstract

Fanconi anemia (FA) is a rare inherited disorder that mainly affects the bone marrow. This condition causes decreased production of all types of blood cells. FA is caused by a defective repair of DNA interstrand crosslinks and to date, mutations in over 20 genes have been linked to the disease. Advances in science and molecular biology have provided new insight between FA gene mutations and the severity of clinical manifestations. Here, we will highlight the current and promising therapeutic options for this rare disease. The current standard treatment for FA patients is hematopoietic stem cell transplantation, a treatment associated to exposure to radiation or chemotherapy, immunological complications, plus opportunistic infections from prolonged immune incompetence or increased risk of morbidity. New arising treatments include gene addition therapy, genome editing using CRISPR-Cas9 nuclease, and hematopoietic stem cell generation from induced pluripotent stem cells. Finally, we will also discuss the revolutionary developments in mRNA therapeutics as an opportunity for this disease.

Trial registration: ClinicalTrials.gov NCT00001399.

Keywords: CRISPR; Fanconi anemia; Genome editing; HCS; mRNA-LNP.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Bone Marrow / metabolism
  • DNA Damage
  • Fanconi Anemia* / diagnosis
  • Fanconi Anemia* / genetics
  • Fanconi Anemia* / therapy
  • Genetic Therapy
  • Hematopoietic Stem Cells / metabolism
  • Humans

Associated data

  • ClinicalTrials.gov/NCT00001399