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Genetic strategies for the treatment of sickle cell anaemia
Author(s) -
MansillaSoto Jorge,
Rivière Isabelle,
Sadelain Michel
Publication year - 2011
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/j.1365-2141.2011.08773.x
Subject(s) - haematopoiesis , stem cell , transplantation , induced pluripotent stem cell , genetic enhancement , immunology , hematopoietic stem cell transplantation , biology , medicine , cancer research , embryonic stem cell , genetics , gene
Summary Sickle cell anaemia is a severe inherited blood disorder for which there is presently no curative therapy other than allogeneic haematopoietic stem cell (HSC) transplantation. This therapeutic option, however, is not available to most patients because of the lack of a matched related donor. Different genetic strategies aiming to treat the anaemia and prevent sickling are under investigation. They include strategies to transfer a regulated globin gene in autologous HSCs–the most developed approach, which is about to undergo clinical evaluation–, and strategies to either restore endogenous HBG expression, repair or eliminate HBB S mutant transcripts, or correct the sickle mutation in HSCs or induced pluripotent stem cells. Their common ultimate goals are to afford therapeutic levels of HbA or HbF in the erythroid progeny of autologous HSCs (sufficient to prevent pathological sickling) and engraft the genetically modified HSCs with minimal short‐term toxicity (primarily caused by the conditioning regimen) and long‐term toxicity (primarily caused by genotoxicity). We discuss here the status of application of these technologies, outlining recent advances and the hurdles that lay ahead.