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High-fidelity PAMless base editing of hematopoietic stem cells to treat chronic granulomatous disease

Bzhilyanskaya, Vera, Ma, Linyuan, Liu, Siyuan, Fox, Lauren R., Whittaker, Madelynn N., Meis, Ronald J., Choi, Uimook, Lawson, Amanda, Ma, Michelle, Theobald, Narda, Burkett, Sandra, Sweeney, Colin L., Lazzarotto, Cicera R., Tsai, Shengdar Q., Lack, Justin B., Wu, Xiaolin, Dahl, Gary A., Malech, Harry L., Kleinstiver, Benjamin P., De Ravin, Suk See·2024·Science Translational Medicine
DOI 10.1126/scitranslmed.adj6779PMC PMC11753194
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Abstract

X-linked chronic granulomatous disease (X-CGD) is an inborn error of immunity (IEI) resulting from genetic mutations in the cytochrome b-245 beta chain ( CYBB ) gene. The applicability of base editors (BEs) to correct mutations that cause X-CGD is constrained by the requirement of Cas enzymes to recognize specific protospacer adjacent motifs (PAMs). Our recently engineered PAMless Cas enzyme, SpRY, can overcome the PAM limitation. However, the efficiency, specificity, and applicability of SpRY-based BEs to correct mutations in human hematopoietic stem and progenitor cells (HSPCs) have not been thoroughly examined. Here, we demonstrated that the adenine BE ABE8e-SpRY can access a range of target sites in HSPCs to correct mutations causative of X-CGD. For the prototypical X-CGD mutation CYBB c.676C>T, ABE8e-SpRY achieved up to 70% correction, reaching efficiencies greater than three-and-one-half times higher than previous CRISPR nuclease and donor template approaches. We profiled potential off-target DNA edits, transcriptome-wide RNA edits, and chromosomal perturbations in base-edited HSPCs, which together revealed minimal off-target or bystander edits. Edited alleles persisted after transplantation of the base-edited HSPCs into immunodeficient mice. Together, these investigational new drug–enabling studies demonstrated efficient and precise correction of an X-CGD mutation with PAMless BEs, supporting a first-in-human clinical trial (NCT06325709) and providing a potential blueprint for treatment of other IEI mutations.

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  1. 10.1126/scitranslmed.aad8856 · DOI · Paper page
  2. 10.1038/s41591-019-0735-5 · DOI · Paper page
  3. 10.1016/j.jaci.2019.03.012 · DOI
  4. 10.1016/S2352-3026(19)30021-3 · DOI
  5. 10.1038/s41467-022-31344-x · DOI · Paper page
  6. 10.1038/3233 · DOI
  7. 10.1038/sj.cgt.7700232 · DOI
  8. 10.1038/s41591-020-0790-y · DOI
  9. 10.1038/s41588-023-01434-7 · DOI
  10. 10.1056/NEJMoa2300709 · DOI
  11. 10.1097/00005792-200005000-00003 · DOI · Paper page
  12. 10.1093/cid/ciu1154 · DOI
  13. 10.1542/peds.114.2.462 · DOI
  14. 10.1038/s41588-021-00838-7 · DOI · Paper page
  15. 10.1038/s41556-019-0425-z · DOI
  16. 10.1038/nbt.4317 · DOI
  17. 10.1038/s41588-020-0623-4 · DOI · Paper page
  18. 10.1038/nbt.4192 · DOI · Paper page
  19. 10.1038/ncomms15178 · DOI
  20. 10.1038/nature24644 · DOI · Paper page
  21. 10.1038/nbt.3803 · DOI · Paper page
  22. 10.1038/nature17946 · DOI · Paper page
  23. 10.1038/s41596-021-00525-1 · DOI
  24. 10.1038/s41573-020-0084-6 · DOI
  25. 10.1126/science.1225829 · DOI · Paper page
  26. 10.1038/nbt.2508 · DOI · Paper page
  27. 10.1038/s41477-020-00827-4 · DOI
  28. 10.1111/pbi.13838 · DOI · Paper page
  29. 10.1038/s41467-022-30228-4 · DOI
  30. 10.1038/s41467-022-31034-8 · DOI
  31. 10.1038/nature16526 · DOI · Paper page
  32. 10.1038/s41587-019-0254-4 · DOI
  33. 10.1016/j.tig.2021.09.002 · DOI
  34. 10.1038/s41587-020-0412-8 · DOI
  35. 10.1007/978-1-0716-2879-9_5 · DOI
  36. 10.1182/blood.2021011192 · DOI
  37. 10.1182/blood.2020008503 · DOI
  38. 10.3389/fgeed.2022.923718 · DOI
  39. 10.1016/j.bbmt.2020.09.031 · DOI
  40. 10.1038/nbt.3290 · DOI · Paper page
  41. 10.1016/j.stem.2010.06.014 · DOI · Paper page
  42. 10.1182/blood.V77.6.1218.1218 · DOI
  43. 10.1084/jem.172.1.363 · DOI
  44. 10.1038/bcj.2011.35 · DOI
  45. 10.1038/s41587-020-0555-7 · DOI
  46. 10.14797/mdcj-10-1-3 · DOI
  47. 10.1038/s41587-024-02142-1 · DOI
  48. 10.1126/scitranslmed.aan0820 · DOI · Paper page
  49. 10.1038/nbt.4172 · DOI · Paper page
  50. 10.1517/14712598.8.6.725 · DOI
  51. 10.1007/s00294-021-01211-1 · DOI
  52. 10.1126/sciadv.aax5717 · DOI
  53. 10.3389/fimmu.2022.1067417 · DOI
  54. 10.1038/s41587-020-0491-6 · DOI
  55. 10.1038/s41587-023-01915-4 · DOI · Paper page
  56. 10.1038/s41586-019-1711-4 · DOI · Paper page
  57. 10.1038/s41576-022-00541-1 · DOI
  58. 10.1038/s41587-023-01947-w · DOI
  59. 10.1038/s41587-024-02324-x · DOI
  60. 10.1038/s41587-019-0032-3 · DOI
  61. 10.1038/s41587-020-0562-8 · DOI
  62. 10.1038/s41587-022-01492-y · DOI
  63. 10.1101/gr.275579.121 · DOI
  64. 10.1038/s41592-018-0051-x · DOI
  65. 10.1186/s13059-016-1029-6 · DOI
  66. 10.1101/861054 · DOI
  67. 10.1038/s41525-021-00227-3 · DOI
  68. 10.1016/0888-7543(92)90147-K · DOI
  69. 10.1002/gcc.2870040311 · DOI

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Metadata

Authors
Bzhilyanskaya, V., Ma, L., Liu, S., Fox, L. R., Whittaker, M. N., Meis, R. J., Choi, U., Lawson, A., Ma, M., Theobald, N., Burkett, S., Sweeney, C. L., Lazzarotto, C. R., Tsai, S. Q., Lack, J. B., Wu, X., Dahl, G. A., Malech, H. L., Kleinstiver, B. P., & De Ravin, S. S.
Affiliations
  • Genetic Immunotherapy Section, Laboratory of Clinical Immunology and Microbiology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
  • Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA 02114, USA.
  • Molecular Cytogenetic Core Facility, Mouse Cancer Genetics Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, MD 21702, USA.
  • CELLSCRIPT, Madison, WI 53713, USA.
  • Department of Hematology, St. Jude Children’s Research Hospital, Memphis, TN 38105, USA.
  • Bioinformatics (NCBR)/Integrated Data Sciences Section (IDSS), Research Technology Branch/DIR/NIAID, Frederick, MD 21702, USA.
ORCID
Venue
Science Translational Medicine
Publisher
American Association for the Advancement of Science (AAAS)
Published
2024-10-16
Volume
16
Issue
769
ISSN
  • 1946-6234
  • 1946-6242
DOI
10.1126/scitranslmed.adj6779
PMC
PMC11753194
Cited by
28
References
14
Language
en

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CoChat. (2026). Citation check: High-fidelity PAMless base editing of hematopoietic stem cells to treat chronic granulomatous disease. https://app.cochat.ai/papers/10.1126/scitranslmed.adj6779
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Bzhilyanskaya, V., Ma, L., Liu, S., Fox, L. R., Whittaker, M. N., Meis, R. J., Choi, U., Lawson, A., Ma, M., Theobald, N., Burkett, S., Sweeney, C. L., Lazzarotto, C. R., Tsai, S. Q., Lack, J. B., Wu, X., Dahl, G. A., Malech, H. L., Kleinstiver, B. P., & De Ravin, S. S. (2024). High-fidelity PAMless base editing of hematopoietic stem cells to treat chronic granulomatous disease. Science Translational Medicine. https://doi.org/10.1126/scitranslmed.adj6779