Project Details
Projekt
In vivo targeting of hematopoietic stem cells to treat sickle cell disease
Applicant
Dr. Denise Klatt
Subject Area
Hematology, Oncology
Term
from 2020 to 2023
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 451828430
Sickle cell disease (SCD) is a frequent blood disorder caused by a single point mutation in the beta-globin gene, with diverse and ultimately life-threatening pathophysiological consequences. The majority of affected individuals lives in developing countries and dies during infancy, but even in western countries the life expectancy and quality of life are significantly reduced. The only curative treatment option for SCD patients has been hematopoietic stem cell (HSC) transplantation, but recently curative ex vivo gene therapy approaches have entered clinical testing with very promising results. The more wide-spread use of gene therapy, either using viral vectors or next generation gene editing approaches, is severely hampered by the complex procedures of ex vivo cell manipulation, the need for myeloablative conditioning and the high per patient costs associated with it. Direct in vivo delivery of a curative payload into HSC would address most of the current limitations and would be a tremendous step forward not only for SCD, but for many severe diseases for which ex vivo HSC approaches are currently being used or developed. The aim of this innovative work is to generate novel strategies for in vivo gene transfer into HSCs using recently described novel viral vector types. The candidate vectors display a strong preference for HSCs, high serum stability and there is no preexisting immunity in humans. Despite the multifaceted challenges, this project builds on my and my host's areas of expertise and is motivated by the tremendous potential and benefit this could bring to patients.
DFG Programme
WBP Fellowship
International Connection
USA
