**10. Acknowledgment**

This work was supported by the Russian Foundation for Basic Research Grants 09-04-01312 to F.R. and 11-04-01814-а to A.B, and a grant of the RAS Program of Molecular Cellular Biology to A.B.

### **11. References**


technique may result in production of bona fide hematopietic stem cells capable of longterm reconstitution, remains to be seen. It should be noted that such a goal has not yet been achieved for ES or iPS cells. If efficient reprogramming into HSCs were possible, the perspectives would look staggering. First of all, since starting primary cell populations such as mesenchymal stem/progenitor cells can be propagated for many generations and are amenable for selection of efficient vector integration events, it will be possible to obtain cell populations in which the majority of reprogrammed HCS-like cells bear functioning transgenes, thus increasing efficiency of gene therapy many-fold. Besides, if this technology were able to generate ex vivo significantly more reprogrammed cells with HSC properties than is possible to obtain from a patient, this would establish basis for a radically increase in a level of chimerism after transplantation, thus further improving the efficiency of gene therapy. Of course, the safety issues, in particular potential epigenetic and genome instability of reprogrammed cells that might result in neoplastic transformations, must be

Current protocols of gene therapy of hematopoietic and immune system, despite significant efforts by numerous teams worldwide, demonstrate as yet a relatively modest clinical efficiency. However, there are sufficient reasons to assume that many rather inconspicuous yet significant recent technical developments are preparing the field for a decisive breakthrough in the near future. In addition, new cutting- edge technologies such as direct cell reprogramming are entering the scene and may eventually present a radically different and a more efficient solution of the problem. Given all these considerations, the future of

This work was supported by the Russian Foundation for Basic Research Grants 09-04-01312 to F.R. and 11-04-01814-а to A.B, and a grant of the RAS Program of Molecular Cellular

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**9. Conclusion** 

**10. Acknowledgment** 

0092-8674

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