Safe and Effective In Vivo Targeting and Gene Editing in Hematopoietic Stem Cells: Strategies for Accelerating Development

Hum Gene Ther. 2021 Jan;32(1-2):31-42. doi: 10.1089/hum.2020.263.


On May 11, 2020, the National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation (Gates Foundation) held an exploratory expert scientific roundtable to inform an NIH-Gates Foundation collaboration on the development of scalable, sustainable, and accessible HIV and sickle cell disease (SCD) therapies based on in vivo gene editing of hematopoietic stem cells (HSCs). A particular emphasis was on how such therapies could be developed for low-resource settings in sub-Saharan Africa. Paula Cannon, PhD, of the University of Southern California and Hans-Peter Kiem, MD, PhD, of the Fred Hutchinson Cancer Research Center served as roundtable cochairs. Welcoming remarks were provided by the leadership of NIH, NHLBI, and BMGF, who cited the importance of assessing the state of the science and charting a path toward finding safe, effective, and durable gene-based therapies for HIV and SCD. These remarks were followed by three sessions in which participants heard presentations on and discussed the therapeutic potential of modified HSCs, leveraging HSC biology and differentiation, and in vivo HSC targeting approaches. This roundtable serves as the beginning of an ongoing discussion among NIH, the Gates Foundation, research and patient communities, and the public at large. As this collaboration progresses, these communities will be engaged as we collectively navigate the complex scientific and ethical issues surrounding in vivo HSC targeting and editing. Summarized excerpts from each of the presentations are given hereunder, reflecting the individual views and perspectives of each presenter.

Keywords: gene editing; in vivo; sickle cell disease; targeting.

MeSH terms

  • Anemia, Sickle Cell*
  • Cell Differentiation
  • Gene Editing*
  • Genetic Therapy
  • Hematopoietic Stem Cells
  • Humans