Prostaglandin E2 Increases Lentiviral Vector Transduction Efficiency of Adult Human Hematopoietic Stem and Progenitor Cells

Mol Ther. 2018 Jan 3;26(1):320-328. doi: 10.1016/j.ymthe.2017.09.025. Epub 2017 Oct 5.


Gene therapy currently in development for hemoglobinopathies utilizes ex vivo lentiviral transduction of CD34+ hematopoietic stem and progenitor cells (HSPCs). A small-molecule screen identified prostaglandin E2 (PGE2) as a positive mediator of lentiviral transduction of CD34+ cells. Supplementation with PGE2 increased lentiviral vector (LVV) transduction of CD34+ cells approximately 2-fold compared to control transduction methods with no effect on cell viability. Transduction efficiency was consistently increased in primary CD34+ cells from multiple normal human donors and from patients with β-thalassemia or sickle cell disease. Notably, PGE2 increased transduction of repopulating human HSPCs in an immune-deficient (nonobese diabetic/severe combined immunodeficiency/interleukin-2 gamma receptor null [NSG]) xenotransplantation mouse model without evidence of in vivo toxicity, lineage bias, or a de novo bias of lentiviral integration sites. These data suggest that PGE2 improves lentiviral transduction and increases vector copy number, therefore resulting in increased transgene expression. As a result, PGE2 may be useful in clinical gene therapy applications using lentivirally modified HSPCs.

Keywords: gene therapy; hematopoietic stem cell; hemoglobinopathy; lentiviral vector; prostaglandin E(2); transduction; vector copy number.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anemia, Sickle Cell / genetics
  • Anemia, Sickle Cell / metabolism
  • Animals
  • Antigens, CD34 / metabolism
  • Cell Line
  • Dinoprostone / metabolism*
  • Gene Library
  • Gene Transfer Techniques
  • Genetic Therapy
  • Genetic Vectors / genetics*
  • Globins / genetics
  • Hematopoietic Stem Cells / metabolism*
  • Humans
  • Lentivirus / genetics*
  • Leukocyte Common Antigens / metabolism
  • Mice
  • Transduction, Genetic*
  • Transgenes
  • Transplantation, Heterologous
  • Virus Internalization
  • beta-Thalassemia / genetics
  • beta-Thalassemia / metabolism


  • Antigens, CD34
  • Globins
  • Leukocyte Common Antigens
  • Dinoprostone