Researchers:
Project Manager:
Zule Romero Garcia
Former Researchers/Collaborators:
Ron Baik
Mandy Boontanrart
Mark DeWitt
Jenny Shin
Jonathan Vu
We are collaborating with clinicians to develop genome editing as a real world therapy to treat sickle cell disease.
Genetic diseases of blood cells are prime candidates for treatment through ex vivo genome editing of hematopoietic stem/progenitor cells (HSPCs). We are working to better understand and develop therapeutic approaches for treating sickle cell disease. Sickle cell disease (SCD) is a recessive genetic disorder caused by a single mutation in the β-globin gene (HBB). Sickle hemoglobin damages red blood cells and distorts them into a “sickle” shape, which leads to painful circulatory blockages, progressive organ damage, and premature death.
We are developing genome editing into a viable therapy for sickle cell patients. We employ a ribonucleoprotein (RNP) complex consisting of Cas9 protein and single guide RNA (sgRNA), together with a single-stranded DNA oligonucleotide donor (ssODN), to enable efficient replacement of the SCD mutation in human HSPCs. We have already achieved successful editing in patient HSPCs, demonstrated safety and efficacy in a mouse model, and are now working towards a human clinical trial.
Magis W, DeWitt MA, Wyman SK, Vu JT, Heo S-J, Shao SJ, Hennig F, Romero ZG, Campo-Fernandez B, Said S, McNeill MS, Rettig GR, Sun Y, Wang Y, Behlke MA, Kohn DB, Boffelli D, Walters MC, Corn JE, and Martin DIK.Ā iScience
(2022)Baik R, Wyman SK, Kabir S, and Corn JE. PLoS One
(2021)Boontanrart MY, Schrƶder MS, Stehli GM, BanoviÄ M, Wyman SK, Lew RJ, Bordi M, Gowen BG, DeWitt MA, and Corn JE. Cell
(2020)DeWitt MA, Magis W, Bray NL, Wang T, Berman JR, Urbinati F, Heo S, Mitros T, Muñoz DP, Boffelli D, Kohn DB, Walters MC, Carroll D, Martin DK, and Corn JE. Science Translational Medicine. Preprint (free to read).
(2016)