Graft-versus-host-disease (GVHD) is a frequent and dangerous complication of allogenic transplantations of bone marrow. Gene therapy offers a way to deal with the problem. It is based on the introduction of suicide genes (SG) into the donor's T lymphocytes, which are responsible for the development of GVHD. If it develops, the presence of SG in the effector cells gives an opportunity to get rid of them, because their products are capable of changing otherwise innocuous substances into highly cytotoxic metabolites. For the transduction of SG retrovirus-based vectors are used. The authors tried to employ for this purpose recombinant adeno-associated viruses (rAAV). The attempt was unsuccessful. When using rAAV as vectors, the efficacy of transduction was very low. Further experiments indicated that this failure was due to the absence of receptor for AAV in T lymphocytes. It seems clear that until the surface of rAAV is modified to facilitate their penetration into T cells, they cannot replace retroviruses for transfer of SG into this cell type.

Ustav hematologie a krevní transfuze Praha