NANOCAST: Nanoparticles for Cas9 targeting in blood stem cells
NANOCAST 1 and 2, in which Erasmus MC, LUMC and Harbour Antibodies join forces, aims to develop an efficient delivery method for the systemic administration of CRISPR genome editing components to blood stem cells
The consortium developed antibodies against human hematopoietic stem cell markers CD34 and Gpr56, cloned into expression vectors and conjugated to nanoparticles encapsulating CRISPR/Cas9. These targeted nanoparticles showed efficient uptake and increased fetal globin expression in vitro, as well as targeted editing in CD34+ and CD34+/Gpr56+ cells without affecting viability. In vivo experiments showed preferential accumulation in bone marrow of sickle cell mice. Results support further development of in vivo targeting and editing.
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