In gene therapy, expression of a corrected gene leads to synthesis of proteins foreign to the immune system. Cells expressing these will therefore be recognized as aberrant and destructed. We used... Show moreIn gene therapy, expression of a corrected gene leads to synthesis of proteins foreign to the immune system. Cells expressing these will therefore be recognized as aberrant and destructed. We used a known immune evasion mechanism to "stealth" transgene products. We fused the coding sequence of the Gly-Ala repeats (GAr) of the Epstein-Barr Virus (EBV) nuclear antigen 1 (EBNA-1) with three different transgenes, i.e. E.coli LacZ, firefly Luciferase and herpes simplex virus 1 thymidine kinase (TK). We show that the EBV GAr system could well be used to prevent the immune system of reacting on transgenes. We could also show, that GAr-TK might be a good candidate to use in bone marrow transplantation protocols. In addition to the GAr, we used an alternative open reading frame found within the ENBA-1 sequence (GZr). We made a fusion of the GZr with the LacZ gene and show that, in contrast to a repeat deleted construct, the construct bearing repeats was protected for recognition by LacZ specific CTLs. This shows that the GZ repeats might be another candidate to shield transgenes for the immune system. The human herpes virus 8 (HHV-8) has a protein like EBNA-1, involved in establishing latency, latency-associated nuclear antigen-1 (LANA-1). We show that LANA-1, like EBNA-1, possesses an immune evasion effect. Show less
