Zhijian Qian, PhD and Wen-Shu Wu, PhD - University of Illinois at Chicago

Zhijian Qian, PhD and Wen-Shu Wu, PhD 

Zhijian Qian, PhD and Wen-Shu Wu, PhD Project Title:

Correction of JAK2 mutation in myeloproliferative neoplasms by gene editing

Focus Area (s):

Gene editing applied to MPNs

Project description:

The aim of this project is to test the feasibility of correcting the JAK2V617F mutation using gene editing technologies and assess those technologies as a therapeutic approach for the treatment of MPNs.

What we expect to learn:

Whether or not gene editing is an option for treating JAK2V617F-mediated MPNs

Project Abstract:

Myeloproliferative neoplasms (MPNs) are groups of hematological diseases that overproduce one or more types of blood cells. The JAK2V617F mutation is the driving mutation for MPNs, causing constitutive activation of JAK2 kinase signaling, present in majority of MPNs. MPNs are transplantable with hematopoietic stem cells (HSCs) harboring JAK2V617F. While JAK2 inhibitors are promising drugs for inhibiting MPNs-induced complications, there is no curative treatment for MPNs. One approach to cure MPNs is to correct the JAK2V617F mutation in MPN-HSCs by gene-editing technologies such as transcription activator-like effector nucleases (TALENs) and dimeric Cas9 RNA-guided FokI nuclease (FokI-dCas9). In this project we will identify safe and effective genome editing approaches for correcting JAK2V617F mutation in HSCs from MPN mouse models and demonstrate therapeutic potential of JAK2V617F-corrected HSCs in mouse models.

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