Using nanoparticles to repair genes in blood stem cells
NANOCAST: Nanoparticles for Cas9 targeting in 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.
Summary
CRISPR genome editing technology has great potential to cure a large variety of human diseases, including those of the blood-forming system. Many still have an unmet medical need, such as sickle cell disease (~300,000 newborn cases annually). The goal is to repair genes in blood stem cells using CRISPR, but in vivo editing remains challenging.
NANOCAST combines nanotechnology and biochemistry to develop targeted in vivo gene repair. The system uses biodegradable nanoparticles (PLGA and lipid-PEG) encapsulating CRISPR guide-RNAs and Cas9 (Erasmus MC) and is guided by antibodies (Harbour Antibodies) to target bone marrow blood stem cells. This approach increases stability, targeting precision, and reduces costs, while being adaptable for multiple diseases.
Technology Readiness Level (TRL)
- 1- 4 -
Time period
27 months
Partners
