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Immune responses to gene therapy vectors in the context of corneal transplantation
Author(s) -
RITTER T,
WILK M,
GONG N,
PLEYER U,
NOSOV M
Publication year - 2009
Publication title -
acta ophthalmologica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.534
H-Index - 87
eISSN - 1755-3768
pISSN - 1755-375X
DOI - 10.1111/j.1755-3768.2009.3462.x
Subject(s) - genetic enhancement , immune system , viral vector , context (archaeology) , transduction (biophysics) , transplantation , immunology , corneal transplantation , vector (molecular biology) , virology , virus , biology , gene delivery , medicine , gene , genetics , paleontology , biochemistry , surgery , recombinant dna
Purpose The genetic engineering of grafts or cells prior to transplantation is an attractive approach to protect the graft from allogeneic rejection. Virus vector‐based gene therapy is a promising method for successful ex‐vivo gene transfer however, the induction of an immune response against gene‐modified tissues raises concern. Methods Different virus families (Adenovirus, Retrovirus, Adeno‐associated virus, Herpesvirus) have been studied as gene therapy vehicles for the delivery of therapeutic molecules. Moreover, different serotypes or envelope proteins have been used to modulate transduction efficiencies of target cells or to evade pre‐existing immunity. Results Here we review gene therapeutic applications using viral vectors in the context of cornea transplantation. Both local and systemic expression of immunomodulatory molecules have led to the prevention of corneal graft rejection. However, different results have been obtained with regard to the induction of immune responses after local or systemic expression of the gene therapy vector. Not surprisingly over‐expression of anti‐inflammatory molecules not only modulated allograft rejection but also influenced the immune response against the viral vector and virally transduced cells. Conclusion Recent clinical trials indicate that the application of viral vectors in ophthalmology is promising however, the generation of immune responses against the viral vector or virally transduced cells are still a serious obstacle for a broader application of gene therapy. Supported by Deutsche Forschungsgemeinschaft (DFG Pl 150/14‐1 and Ri 764/10‐1) and Science Foundation of Ireland (SFI 06/RFP/BIC056 and SFI 07/IN.1/B925)