Lentiviral-Mediated Gene Therapy in Fanconi Anemia-A Mice Reveals Long-Term Engraftment and Continuous Turnover of Corrected HSCs

Hematopoietic cell transplantation in Fanconi anemia: current evidence, challenges and recommendations

“…Studies of gene therapy in murine models of FA [93] and with human FA cell lines [94] are ongoing with some promising results. Proceedings of the 1 st International Fanconi Anemia Gene Therapy Working Group Meeting from November 2010 outlines expert opinions on optimal strategies for proceeding to clinical trials, including details on vector design, hematopoietic cell preparation, and methods of transduction [95].…”

Elevated FANCA expression determines a worse prognosis in chronic lymphocytic leukemia and interferes with p53 function

“…Indeed, this cellular phenotype is behind the progressive hematopoietic progenitor cell depletion in patients with FA (18). This fact provides the proliferative advantage to the genetically corrected cells that allows the use of gene therapy in the treatment of patients with Fanconi anemia (25). CLL represents a somehow opposite situation, with the accumulation of cells incapable of being autoeliminated because of a failure in their apoptosis machinery (26).…”

Minimal conditioning in Fanconi anemia promotes multi‐lineage marrow engraftment at 10‐fold lower cell doses

“…For FA patients, these autologous transplants are typically performed in expedited protocols minimizing the time that the patient's cells are cultured and exposed to oxidative stress ex vivo because this can lead to additional accrued DNA damage . Because corrected FA cells are known to have a selective advantage in vivo, conditioning may not be required and has not been used in the autologous gene therapy setting.…”