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由组氨酸接枝聚 (β-氨基酯) 酯纳米矢量为媒介对髓样分化因子 88 信号的抑制，可诱导供体特异性异体移植物肝耐受性

 

Authors Hu F, Wang H, Zhang S, Peng Y, Su L, Chang J, Liu G

Published Date July 2015 Volume 2015:10 Pages 4367—4382

DOI http://dx.doi.org/10.2147/IJN.S81413

Received 23 January 2015, Accepted 28 March 2015, Published 6 July 2015

Approved for publication by Dr Lei Yang

Abstract: Toll-like receptors (TLRs ) activate biochemical pathways that evoke activation of innate immunity, which leads to dendritic cell maturation and initiation of adaptive immune responses that provoke allograft rejection. We aimed to prolong allograft survival by selectively inhibiting expression of myeloid differentiation factor 88 (MyD88 ), which is an essential adaptor in TLR signaling. We designed and synthesized a novel histidine-grafted poly(β-amino ester)(HGPAE) nanovector, which was shown to be safe and efficient both in vitro and in vivo for the delivery of a plasmid containing shRNA targeting MyD88  (pMyD88). We also demonstrated that the pMyD88/HGPAE complex mediated remarkable inhibition of MyD88  expression in rat liver in vivo. We transplanted Dark Agouti rat livers lacking MyD88  as result of transfection with the pMyD88/HGPAE complex into Lewis rats. The recipients survived longer and graft rejection of the donor liver as well as serum levels of IL-2 and IFN-γ in the recipient were significantly reduced.
Keywords: immune recognition, allograft rejection, MyD88 , short hairpin RNA (shRNA), gene delivery, PAE






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