Genetic strategies for the treatment of sickle cell anaemia Journal Article


Authors: Mansilla-Soto, J.; Riviere, I.; Sadelain, M.
Article Title: Genetic strategies for the treatment of sickle cell anaemia
Abstract: 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 HBBS 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. © 2011 Blackwell Publishing Ltd.
Keywords: unclassified drug; review; nonhuman; homologous recombination; cell cycle s phase; gene overexpression; gene expression; erythropoiesis; gene locus; intron; genetic transcription; bacterial artificial chromosome; gene transfer; chimera; gene mapping; homozygosity; cord blood stem cell transplantation; dna; polymerization; gene therapy; globin; lentivirus vector; retrovirus vector; globin gene; transgene; stem cells; allogeneic hematopoietic stem cell transplantation; nuclease; zinc finger nuclease; mean corpuscular volume; hematopoiesis; 3' untranslated region; gene induction; graft rejection; bone marrow transplantation; oligonucleotide; severe combined immunodeficiency; mutagenesis; reticulocyte count; protein dna interaction; sickle cell anemia; psoralen; polyadenylation; lentiviral vector; wiskott aldrich syndrome; transcription activator like effector nuclease; biodegradability; blood viscosity; murine leukemia virus
Journal Title: British Journal of Haematology
Volume: 154
Issue: 6
ISSN: 0007-1048
Publisher: John Wiley & Sons  
Date Published: 2011-06-28
Start Page: 715
End Page: 727
Language: English
DOI: 10.1111/j.1365-2141.2011.08773.x
PROVIDER: scopus
PUBMED: 21707580
DOI/URL:
Notes: --- - "Export Date: 3 October 2011" - "CODEN: BJHEA" - "Source: Scopus"
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MSK Authors
  1. Michel W J Sadelain
    462 Sadelain
  2. Isabelle C Riviere
    168 Riviere