Western countries, GD type 1 (GD1) is the most common phenotype (~94% of patients) and typically manifests with hepatosplenomegaly, bone disease, cytopenias, and variably with Major clinical types delineated by the presence (types 2 and 3) orĪbsence (type 1) of central nervous system involvement areĬommonly used for determining prognosis and management2.
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GD encompasses a spectrum of clinical findingsįrom a perinatal-lethal form to mildly symptomatic forms. (GCase) deficiency and the accumulation of glycolipids inĬell types with high-glycolipid degradation burden, especially ✉email: COMMUNICATIONS | (2020)11:3327 | | 1Īucher disease (GD) is genetic disorder caused by mutations in the GBA gene that result in glucocerebrosidase 4These authors contributed equally: Samantha G. 3 Department of Pathology, Stanford University School of Medicine, Stanford, CA, USA. 2 Gene Therapy Center, Hospital de Clinicas de Porto Alegre, PortoĪlegre, Brazil. Furthermore, it constitutes an adaptable platform for otherġ Department of Pediatrics, Stanford University School of Medicine, Stanford, CA, USA.
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The combination of a safe-harbor and a lineage-specific promoter establishesĪ universal correction strategy and circumvents potential toxicity of ectopic glucocerebrosidase in the stem cells.
#Snapgene p2a serial#
Maintain long-term repopulation and multi-lineage differentiation potential with serial The targeted cells generate glucocerebroside-expressing macrophages and Here, we report an efficient CRISPR/Cas9-basedĪpproach that targets glucocerebrosidase expression cassettes with a monocyte/macrophage-specific element to the CCR5 safe-harbor locus in human hematopoietic stem and Potential one-time therapy for this disease. Glucocerebrosidase expression, thereby replacing the affected cells, and constituting a Of recombinant glucocerebroside and orally-available glucosylceramide synthase inhibitors.Īn alternative approach is to engineer the patient’s own hematopoietic system to restore Current therapies for Gaucher disease include life−long intravenous administration Its hallmark manifestations are attributed to infiltration and inflammation by macrophages. Gaucher disease is a lysosomal storage disorder caused by insufficient glucocerebrosideĪctivity.
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Lucot 3, Pasqualina Colella 1,Īdam Sheikali1, Thomas J. Scharenberg 1,4, Edina Poletto 2,4, Katherine L. Hematopoietic stem cells using genome editing