Abstract
Kidney transplantation remains the best therapeutic option for patients with end-stage renal disease. Immunosuppressive therapy has largely resolved the issue of acute transplant rejection. However, because of its systemic nature, immunosuppressive therapy trades off efficacy against side-effects and its chronic use has been associated with severe infections and malignancy. Moreover, long-term survival of renal grafts did not change over the past twenty years. This situation may be improved by using gene therapy as an alternative or add-on strategy to the classic, systemic immune suppression. This review discusses gene therapy approaches in kidney transplantation by addressing the essentials of delivery vectors and by outlining strategies to achieve local immunosupression and allograft-specific tolerance, both in acute rejection and chronic transplant dysfunction. Employing such strategies, local suppression of the immune response and induction of transplantation-specific tolerance have been accomplished in experimental gene therapy. If successful in the clinical setting, gene therapy may (partially) substitute systemic, non-selective immunosuppressive medication, with a major impact on the quality of life and survival of the transplanted patients as well as on the waiting time for receiving a renal graft.
| Original language | English |
|---|---|
| Pages (from-to) | 1358-1368 |
| Number of pages | 11 |
| Journal | Advanced Drug Delivery Reviews |
| Volume | 62 |
| Issue number | 14 |
| DOIs | |
| Publication status | Published - Nov 30 2010 |
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Keywords
- Gene delivery
- Kidney transplantation
- Liposome
- Plasmid
- Rejection
- Small interfering RNA
- Tolerance
- Virus
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Towards graft-specific immune suppression : Gene therapy of the transplanted kidney. / Sandovici, Maria; Deelman, Leo E.; Benigni, Ariela; Henning, Robert H.
In: Advanced Drug Delivery Reviews, Vol. 62, No. 14, 30.11.2010, p. 1358-1368.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Towards graft-specific immune suppression
T2 - Gene therapy of the transplanted kidney
AU - Sandovici, Maria
AU - Deelman, Leo E.
AU - Benigni, Ariela
AU - Henning, Robert H.
PY - 2010/11/30
Y1 - 2010/11/30
N2 - Kidney transplantation remains the best therapeutic option for patients with end-stage renal disease. Immunosuppressive therapy has largely resolved the issue of acute transplant rejection. However, because of its systemic nature, immunosuppressive therapy trades off efficacy against side-effects and its chronic use has been associated with severe infections and malignancy. Moreover, long-term survival of renal grafts did not change over the past twenty years. This situation may be improved by using gene therapy as an alternative or add-on strategy to the classic, systemic immune suppression. This review discusses gene therapy approaches in kidney transplantation by addressing the essentials of delivery vectors and by outlining strategies to achieve local immunosupression and allograft-specific tolerance, both in acute rejection and chronic transplant dysfunction. Employing such strategies, local suppression of the immune response and induction of transplantation-specific tolerance have been accomplished in experimental gene therapy. If successful in the clinical setting, gene therapy may (partially) substitute systemic, non-selective immunosuppressive medication, with a major impact on the quality of life and survival of the transplanted patients as well as on the waiting time for receiving a renal graft.
AB - Kidney transplantation remains the best therapeutic option for patients with end-stage renal disease. Immunosuppressive therapy has largely resolved the issue of acute transplant rejection. However, because of its systemic nature, immunosuppressive therapy trades off efficacy against side-effects and its chronic use has been associated with severe infections and malignancy. Moreover, long-term survival of renal grafts did not change over the past twenty years. This situation may be improved by using gene therapy as an alternative or add-on strategy to the classic, systemic immune suppression. This review discusses gene therapy approaches in kidney transplantation by addressing the essentials of delivery vectors and by outlining strategies to achieve local immunosupression and allograft-specific tolerance, both in acute rejection and chronic transplant dysfunction. Employing such strategies, local suppression of the immune response and induction of transplantation-specific tolerance have been accomplished in experimental gene therapy. If successful in the clinical setting, gene therapy may (partially) substitute systemic, non-selective immunosuppressive medication, with a major impact on the quality of life and survival of the transplanted patients as well as on the waiting time for receiving a renal graft.
KW - Gene delivery
KW - Kidney transplantation
KW - Liposome
KW - Plasmid
KW - Rejection
KW - Small interfering RNA
KW - Tolerance
KW - Virus
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UR - http://www.scopus.com/inward/citedby.url?scp=78649445784&partnerID=8YFLogxK
U2 - 10.1016/j.addr.2010.07.010
DO - 10.1016/j.addr.2010.07.010
M3 - Article
C2 - 20688115
AN - SCOPUS:78649445784
VL - 62
SP - 1358
EP - 1368
JO - Advanced Drug Delivery Reviews
JF - Advanced Drug Delivery Reviews
SN - 0169-409X
IS - 14
ER -