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Transplant engineering

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Transplant engineering (or allograft engineering) is a variant of genetic organ engineering which comprises allograft, autograft and xenograft engineering. In allograft engineering the graft is substantially modified by altering its genetic composition. The genetic modification can be permanent or transient. The aim of modifying the allograft is usually the mitigation of immunological graft rejection.

History

Transient genetic allograft engineering has been pioneered by Shaf Keshavjee and Marcelo Cypel at University Health Network in Toronto by adenoviral transduction for transgenic expression of the IL-10 gene. Permanent genetic allograft engineering has first been done by Rainer Blasczyk and Constanca Figueiredo at Hannover Medical School in Hanover by lentiviral transduction for knocking down MHC expression in pigs (lung) and rats (kidney).

References

  1. Cypel, Marcelo; Liu, Mingyao; Rubacha, Matt; Yeung, Jonathan C.; Hirayama, Shin; Anraku, Masaki; Sato, Masaaki; Medin, Jeffrey; Davidson, Beverly L.; Perrot, Marc de; Waddell, Thomas K. (2009-10-28). "Functional Repair of Human Donor Lungs by IL-10 Gene Therapy". Science Translational Medicine. 1 (4): 4ra9. doi:10.1126/scitranslmed.3000266. ISSN 1946-6234. PMID 20368171. S2CID 13366956.
  2. Machuca, Tiago N.; Cypel, Marcelo; Bonato, Riccardo; Yeung, Jonathan C.; Chun, Yi-Min; Juvet, Stephen; Guan, Zehong; Hwang, David M.; Chen, Manyin; Saito, Tomohito; Harmantas, Constantine (2017-09-01). "Safety and Efficacy of Ex Vivo Donor Lung Adenoviral IL-10 Gene Therapy in a Large Animal Lung Transplant Survival Model". Human Gene Therapy. 28 (9): 757–765. doi:10.1089/hum.2016.070. ISSN 1043-0342. PMID 28052693.
  3. Figueiredo, Constanca; Carvalho Oliveira, Marco; Chen-Wacker, Chen; Jansson, Katharina; Höffler, Klaus; Yuzefovych, Yuliia; Pogozhykh, Olena; Jin, Zhu; Kühnel, Mark; Jonigk, Danny; Wiegmann, Bettina (2019-04-04). "Immunoengineering of the Vascular Endothelium to Silence MHC Expression During Normothermic Ex Vivo Lung Perfusion". Human Gene Therapy. 30 (4): 485–496. doi:10.1089/hum.2018.117. ISSN 1043-0342. PMID 30261752.
  4. Yuzefovych, Yuliia; Valdivia, Emilio; Rong, Song; Hack, Franziska; Rother, Tamina; Schmitz, Jessica; Bräsen, Jan Hinrich; Wedekind, Dirk; Moers, Cyril; Wenzel, Nadine; Gueler, Faikah (2020). "Genetic Engineering of the Kidney to Permanently Silence MHC Transcripts During ex vivo Organ Perfusion". Frontiers in Immunology. 11: 265. doi:10.3389/fimmu.2020.00265. ISSN 1664-3224. PMC 7042208. PMID 32140158.


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