Silencing organ immunogenicity. Is immunosuppression soon to be obsolete?
Interesting results from Hannover suggest that the use of short fragments of RNA to silence the major histocompatibility antigens (MHC) and associated minor antigens of donor lungs during ex-vivo lung perfusion (EVLP) may well be a future game changer in the quest to substantially reduce the need for post-transplant immunosuppression.
Figueiredo et al (1) aimed at reducing the immunogenicity of the porcine lung by silencing MHC expression on the endothelium using a viral vector to deliver short RNA fragments to target antigenic MHC epitopes thereby permanently silencing Swine Leukocyte Antigen I and II expression. This was apparently achieved without affecting cell viability or tissue integrity. The authors comment, “This decrease of immunogenicity carries the potential to generate immunologically invisible organs to counteract the burden of rejection and immunosuppression.”
If these initial findings are substantiated by later studies, the implications are quite revolutionary.
- Figueiredo C et al, Immunoengineering of the vascular endothelium to silence MHC expression during normothermic ex vivo lung perfusion. Hum Gene Ther. 2018 Sep 27. doi: 10.1089/hum.2018.117 (link to abstract)
Xvivo Insights PB-2018-11-07