Modelling osteogenesis of Snyder-Robinson patients by targeting Spermine Synthase using CRISPR/Cas9 in human bone marrow derived mesenchymal stem cells

PI: Fernando A. Fierro, PhD

Institution: University of California, Davis

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Snyder-Robinson Syndrome (SRS) is a rare condition in which patients harbor mutations in the Spermine Synthase (SMS) gene and suffer from thin and fragile bones. This bone deficiency was associated with the inability of a type of stem cell in the bone marrow (commonly called mesenchymal stem cell; MSC) to become, osteoblasts, the cell type responsible for calcium precipitation. Hence, our primary goal is to elucidate why MSC with a dysfunctional SMS gene cannot become normal, mature osteoblasts.

To obtain MSC from SRS patients is challenging, because the cases are extremely rare, and the procedure to isolate the cells is quite invasive, involving drilling into the bone marrow. We are therefore using recently developed gene editing tools to mimic mutations previously described in SRS patients in normal MSC (derived from healthy donors). We will also delete the entire SRS gene. We will then study the cells harboring the SRS mutations in the context of bone formation, comparing them to MSC without mutations. We aim to identify with great precision what alterations occur, in order to identify potential targets to treat the bone defects of SRS patients.