Grant Award Details
To create CRISPR/Cas9 reagents that are capable of generating and reverting MPN associated mutations in various cell types, including primary human hematopoietic stem cells (HSCs).
Grant Application Details
- Genome editing for causation and reversion of MPN-associated mutations in human hematopoietic stem cells
Use gene editing to create tools for the study of mechanisms by which patient-observed mutations lead to myeloproliferative neoplasms.
Editing reagents will yield new insight into how acquired MPN-associated mutations cause disease by overproduction of various cell types and pave the way for gene editing therapies to reverse MPNs.
Major Proposed Activities
- Develop tools to enable the study of MPN-associated mutations at endogenous loci.
- Create isogenic human cell lines harboring MPN-associated mutations and introduce mutations to primary human CD34+ HSCs.
The research described in this proposal will both yield new information to the MPN family of hematopoietic disorders and broadly enable the creation and reversion of mutations in hematopoietic stem cells. New understanding of MPNs could lead to improved drugs to treat these disorders. Methods to perform gene editing in hematopoietic stem cells could be transformative for the treatment of inherited and acquired blood diseases, potentially allowing gene editing therapies to cure such disorders.