Gene Therapy for Graft-versus-Host-Disease

Overview

Graft-versus-host-disease (GVHD) is a frequent and dangerous complication of allogenic transplantations of bonemarrow. Gene therapy offers a way to deal with the problem. It is based on the introduction of suicide genes (SG)into the donor´s Tl ymphocytes, which are responsible for the development of GVHD. If it develops, the presenceof SG in the effector cells gives an opportunity to get rid of them, because their products are capable of changingotherwise innocuous substances into highly cytotoxic metabolites. For the transduction of SG retrovirus-based vectorsare used. The authors tried to employ for this purpose recombinant adeno-associated viruses (rAAV). The attemptwas unsuccessful. When using rAAV as vectors, the efficacy of transduction was very low. Further experimentsindicated that this failure was dueto the absence ofreceptor for AAV in Tlymphocytes. It seems clear that until thesurface of rAAV is modified to facilitate their penetration into Tc ells, they cannot replace retroviruses for transferof SG into this cell type.

Key words:
gene therapy, GVHD, AAV.