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Emerging Infectious Diseases
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Ephrin B2 Targeting

Targeting EphrinB2+ stem cells and interrogating the EphrinB2-Eph axis in pluripotent stem cell fate and differentiation

EphrinB2 is present on murine embryonic stem cells (ESC), hematopoietic stem cells (HSC), and neural stem cells (NSC), and has been previously described as a putative molecular marker of "stemness"1. In collaboration with stem cell biologists, we have developed an armamentarium of tools based on the picomolar affinity of NiV-G for EphrinB2 to interrogate the role of ephrinB2 in human pluripotent stem cell fate and differentiation. In addition, in collaboration with gene therapists, we are developing Nipah virus Env pseudotyped lentiviral vectors that can cross the blood brain barrier and target the CNS. Our initial efforts are encouraging (see K Palomares et al, 2012)2 and show that NiV Env pseudotypes can not only target specific populations of human ESC, HSC, and NSC in vitro, but when administered intravenously in vivo, can bypass the liver sink, a critical barrier in targeted gene delivery. Click here for a more detailed description of our human pluripotent stem cell work that is funded by the California Institute of Regenerative Medicine.

References

  1. Ivanova, N. B. et al. A stem cell molecular signature. Science 298, 601-604, doi:10.1126/science.1073823 (2002).
  2. Karina Palomares et al. Nipah virus envelope pseudotyped lentiviruses efficiently target ephrinB2+ stem cell populations in vitro and bypass the liver sink when administered in vivo. Journal of Virology in press (2012).