Optimal modes and targets of gene therapy in transplantation

Genetic modification strategies have the potential to improve outcome following cell/organ transplantation. A unique opportunity in transplantation is that gene therapies need not be restricted to in vivo approaches and that ex vivo genetic modification of cell and/or organs can be of value. Improvements in vector design, production, and delivery should enhance transfection efficiency and optimize gene expression. Herein, we discuss potential modes of gene therapy, focusing on viral, liposome, or naked DNA-based systems for gene delivery. We suggest gene therapy targets taking into consideration the essential constituents of anti-allograft repertory. In addition to strategies that may have salutary effects in mitigating the threat of acute rejection, we suggest genetic strategies for minimizing ischemia/reperfusion injury as well as for the perennial problem of progressive functional loss of the transplanted organ. Data from pre-clinical transplant models support the idea that gene therapy may improve allograft function and survival. We are optimistic that gene therapy will be of clinical value in the near future in the management of recipients of allografts; we believe that genetic strategies would be essential for successful breaching of the formidable challenge of xenotransplantation.