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From Mendel to a Mendelian disorder: towards a cure for sickle cell disease

In celebrating the bicentenary of Gregor Mendel’s birth, we reflect on progress and future directions in the application of genetics and genomics to delivering a cure for sickle cell disease, a classic Mendelian disorder that affects 5 million people globally, most of whom are in Africa.

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References

  1. Pauling, L., Itano, H. A., Singer, S. J. & Wells, I. C. Sickle cell anemia a molecular disease. Science 110, 543–548 (1949).

    CAS  Article  Google Scholar 

  2. Sankaran, V. G. et al. A functional element necessary for fetal hemoglobin silencing. N. Engl. J. Med. 365, 807–814 (2011).

    CAS  Article  Google Scholar 

  3. Mtatiro, S. N. et al. Genetic variants at HbF-modifier loci moderate anemia and leukocytosis in sickle cell disease in Tanzania. Am. J. Hematol. 90, E1–E4 (2015).

    CAS  Article  Google Scholar 

  4. Collins, F. S., Green, E. D., Guttmacher, A. E., Guyer, M. S. & The US National Genomi Research Institute. A vision for the future of genomics research. Nature 422, 835–847 (2003).

    CAS  Article  Google Scholar 

  5. Tishkoff, S. A. & Kidd, K. K. Implications of biogeography of human populations for ‘race’ and medicine. Nat. Genet. 36, S21–S27 (2004).

    CAS  Article  Google Scholar 

  6. Consortium, H. A. et al. Research capacity. Enabling the genomic revolution in Africa. Science 344, 1346–1348 (2014).

    Article  Google Scholar 

  7. Makani, J. & Luzzatto, L. Of mice and men: from hematopoiesis in mouse models to curative gene therapy for sickle cell disease. Cell 185, 1261–1265 (2022).

    CAS  Article  Google Scholar 

  8. Ribeil, J. A. et al. Gene therapy in a patient with sickle cell disease. N. Engl. J. Med. 376, 848–855 (2017).

    CAS  Article  Google Scholar 

  9. Esrick, E. B. et al. Post-transcriptional genetic silencing of BCL11A to treat sickle cell disease. N. Engl. J. Med. 384, 205–215 (2021).

    CAS  Article  Google Scholar 

  10. Frangoul, H. et al. CRISPR–Cas9 gene editing for sickle cell disease and beta-thalassemia. N. Engl. J. Med. 384, 252–260 (2021).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank all those from whom we have learned genetics, all those who have made advances in gene therapy, and all of our patients with sickle cell disease.

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Correspondence to Julie Makani.

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Makani, J., Nkya, S., Collins, F. et al. From Mendel to a Mendelian disorder: towards a cure for sickle cell disease. Nat Rev Genet 23, 389–390 (2022). https://doi.org/10.1038/s41576-022-00498-1

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  • DOI: https://doi.org/10.1038/s41576-022-00498-1

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