Alternative possibilities for correction and prevention of hereditary and congenital pathologies by reprogramming cells in vivo using total RNA of lymphocytes from healthy individuals

Abstract

Previously we have presented an analysis of the relationship between the pathogenesis of various diseases and disorders of the regulatory morphogenetic function of T-lymphocytes. In various experimental models, it was proven that the regenerative effects caused by the adoptive transfer of lymphoid cells from healthy individuals were reproduced to an excellent degree by a total RNA fraction isolated from these cells, that has neither allogeneic nor xenogeneic restrictions. Thus, the problem of histocompatibility was solved to provide extensive opportunities for using the regenerative function of lymphocytes in medicine. It was shown that preparations of total RNA from lymphocytes of healthy individuals contribute to the “reprogramming” of recipient’s lymphocytes, their normalization and, accordingly, the restoration of functions impaired in experimental animals. Along with this, data from more than half a century ago indicated a possibility of complete correction of hereditary pathologies (such as osteopetrosis or marble bone disease, macrocytic anemia, hemophilia A, diabetes mellitus, and general growth retardation in dwarfism) by spleen transplantation or adoptive transfer of lymphocytes from healthy siblings to sub-lethally irradiated model animal recipients. In the clinic, attempts of allogeneic spleen transplantation for the treatment of hemophilia A and Gaucher disease led to a severe complication in the form of graft-versus-host disease mediated by T lymphocytes of the donor spleen. Therefore, for the purposes of treatment and prevention in cases of increased risk for developing hereditary pathologies in newborns, it can be recommended for clinical trials to use preparations of total RNA from the bone marrow, spleen, thymus from a young healthy mammal or peripheral blood lymphocytes from a young healthy donor, placental or umbilical RNA that contain an optimal ratio of normally functioning subpopulations of lymphocytes to provide a comprehensive therapeutic effect.