• Tarantal, Alice F (PI)
  • Gruenert, Dieter (PI)
  • Muench, Marcus (PI)
  • Peidong, Fan (PI)
  • Chang, Judy (PI)
  • Groudine, Mark (PI)
  • Linial, Maxine (PI)
  • Hoffman, Ronald (PI)
  • Epstein, Charles (PI)
  • Chehab, Farid (PI)
  • Gaensler, Karin (PI)
  • Kan, Yuet (PI)

Project: Research project

Project Details


Sickle Cell Anemia is one of the most common genetic diseases world-wide,
estimated to affect one in 600 new births in African-Americans. Progress
in the management of the disease have improved the quality of life in some
patients, however a curative treatment is not yet available. With the
advent in gene transfer technology, gene therapy is under clinical trial
for several genetic and neoplastic diseases. However, more research is
needed for gene therapy in sickle cell anemia because it is necessary to
insert genes into pluripotent hematopoietic stem cells and to carry a gene
that is expressed at a high level to inhibit the sickling process. It is
the purpose of this program project to address these problems with a group
of complementary projects. Based on recent findings that retroviral
infection can be made to be tissue-specific by means of ligand receptor
interaction, vectors will be constructed to infect hematopoietic stem
cells through interaction with cKit and CD34. As the present retroviral
vectors are produced at relatively low titer, novel retroviral vectors
with either two to three logs higher titer will be tested. To improve the
chance of transducing pluripotent stem cells, retroviral vectors which can
integrate into non-dividing cells will be designed. As liposomes can
deliver DNA to many cells, this vehicle will also be explored as a means
of targeting hematopoietic tissue. To pave the way for future gene therapy
protocols, experiments will be performed to determine the best source of
hematopoietic stem cell in patients with sickle cell anemia. Since patient
trials with various treatment modalities must be preceded by animal
experimentation, a concerted effort will be made to produce a mouse model
which carries the sickle hemoglobin as the major hemoglobin in the adult.
To support these projects are a DNA/viral core, a stem cell core, and an
animal core. The program has recruited three pilot projects investigating
the transduction of fetal rhesus monkey hematopoietic cells, homologous
recombination approach to replace the beta-S globin gene, and drug testing
mouse models to increase fetal hemoglobin.
Effective start/end date9/30/948/31/07


  • National Institutes of Health
  • National Institutes of Health
  • National Institutes of Health


  • Medicine(all)


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