Journal article

A Combined In Vivo HSC Transduction/Selection Approach Results in Efficient and Stable Gene Expression in Peripheral Blood Cells in Mice

Hongjie Wang, Maximilian Richter, Nikoletta Psatha, Chang Li, Jiho Kim, Jing Liu, Anja Ehrhardt, Susan K Nilsson, Benjamin Cao, Donna Palmer, Philip Ng, Zsuzsanna Izsvak, Kevin G Haworth, Hans-Peter Kiem, Thalia Papayannopoulou, Andre Lieber

MOLECULAR THERAPY-METHODS & CLINICAL DEVELOPMENT | CELL PRESS | Published : 2018

Abstract

We recently reported on an in vivo hematopoietic stem cell (HSC) gene therapy approach. It involves the subcutaneous injections of G-CSF/AMD3100 to mobilize HSCs from the bone marrow into the peripheral blood stream and the intravenous injection of an integrating helper-dependent adenovirus vector system. HSCs transduced in the periphery homed back to the bone marrow, where they persisted long-term. However, high transgene marking rates found in primitive bone marrow HSCs were not reflected in peripheral blood cells. Here, we tested small-molecule drugs to achieve selective mobilization and transduction of HSCs. We found more efficient GFP marking in bone marrow HSCs but no increased marking..

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University of Melbourne Researchers

Grants

Awarded by NIH


Awarded by NATIONAL CANCER INSTITUTE


Awarded by NATIONAL HEART, LUNG, AND BLOOD INSTITUTE


Awarded by NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES


Funding Acknowledgements

The study was supported by grants from the NIH (R21-CA193077, R01-HL128288-01), a grant from the "Wings of Karen" Foundation, a grant from the Marsha Rivkin Foundation, and a grant from the Fred Hutchinson Cancer Research Center STTR program (to A.L.). M.R. was supported through a scholarship from the German Academic Exchange Service (DAAD). J.L. was supported through a scholarship from the Chinese Scholarship Council.