Periodic Reporting for period 1 - RNable (RNA and Nanotechnology Enable Wider Accessibility to Stem Cell Transplantation)
Okres sprawozdawczy: 2022-09-01 do 2024-02-29
Every year, more than 50 000 patients receive blood stem cell transplantation as a curative treatment for diseases such as leukemia, immune deficiencies, and sickle cell anemia. For a successful transplantation, a matching donor who is willing to donate blood stem cells needs to be found. Worldwide, around 30% patients in need of a transplantation cannot find a suitable donor. Umbilical cord blood (UCB) is an easily obtainable alternative source of blood stem cells, but unfortunately most UCB units do not contain enough stem cells for a successful transplantation, which is why UCB is currently only rarely used in the clinic. Within the ERC project UNEXPECTED, we have identified several small RNA biomolecules that can be used to expand engraftable blood stem cells efficiently. However, it is difficult to safely deliver molecules to blood stem cells, and currently used methods are highly toxic. We recently applied cutting edge nanotechnology to solve this long-standing problem in stem cell biology. We established nanostraws as an efficient and gentle alternative delivery method with which both cell function and viability are fully maintained. Our method that allows efficient non-toxic delivery of blood stem cell-expanding RNAs will allow us to greatly increase the number of UCB units that can be used for transplantations. Our approach could provide a life-saving treatment option for the thousands of patients yearly with malignant or inherited diseases that currently are ineligible for a stem cell transplantation procedure.
A large number of siRNAs were screened in functional assays for their ability of expand the number human hematopoietic stem and progenitor cells (HSPCs). One particularly potent siRNA was identified that upon nanostraw-mediated delivery conferred substantial expansion of human HSPCs as assessed in vitro. Moreover in vivo transplantation assays in xenograft models indicated enhanced long term engraftment of siRNA-treated HSPCs compared to controls. Molecular assays including RNA sequencing have been performed on siRNA treated HSPCs to enable a detailed safety assessment withj promising outcomes. Currently work is undertaken to explore IP framework around the siRNA for subsequent patent application.
Our concept of gentle nanostraw-mediated delivery of potent small RNA molecules to transiently promote expansion of transplanatable stem cells is highlly novel and may signficantly impact clinical medicine in the future. Current actions are focused on securing IP and exploiting the technology further into a product that eventually may reach patients in need of stem cell transplantation.