Therapeutic Gene Editing for Severe Congenital Neutropenia
Background
Severe congenital neutropenia (SCN) is a rare inherited disorder characterized by low absolute neutrophil counts which increases the risk of life-threatening infections. Occurrence of SCN is attributed to changes in various genes, but an estimated 50% of severe congenital neutropenia changes happen in the ELANE gene.
Currently, there are two therapies available to SCN patients, but these treatments have limitations. Most patient benefit from G-CSF treatment but it requires lifelong treatment with regular subcutaneous infusions. Nonetheless in these patients there remains a predisposition to myelodysplastic syndrome and acute myeloid leukemia. The second, and only currently available curative option, is allogeneic hematopoietic stem cell transplant, which is limited by donor availability and immune incompatibility with risk of graft rejection and graft-versus-host-disease.
Technology Overview
Boston Children’s Hospital researchers have developed a universal therapeutic gene editing strategy for treating SCN and potentially other diseases associated with abnormal ELANE gene expression using a novel gene editing agent that targets the ELANE gene. BCH researchers have demonstrated the utility of novel guide RNAs in CRISPR/Cas9 system to produce engineered human hematopoietic stem and progenitor cells with decreased ELANE protein expression.
Benefits
- One-time therapy
- Simple, and highly efficient compared to other treatment strategies
Applications
- Treatment for severe congenital neutropenia
- Potential application for other disorders associated with abnormal ELANE gene expression
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