In vivo self-assembled siRNA as a modality for combination therapy of ulcerative colitis.
In vivo self-assembled siRNA as a modality for combination therapy of ulcerative colitis.
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体内自组装 siRNA 作为溃疡性结肠炎联合治疗的一种方式
DOI：
10.1038/s41467-022-33436-0
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发表时间：
2022-09-28
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
Given the complex nature of ulcerative colitis, combination therapy targeting multiple pathogenic genes and pathways of ulcerative colitis may be required. Unfortunately, current therapeutic strategies are usually based on independent chemical compounds or monoclonal antibodies, and the full potential of combination therapy has not yet been realized for the treatment of ulcerative colitis. Here, we develop a synthetic biology strategy that integrates the naturally existing circulating system of small extracellular vesicles with artificial genetic circuits to reprogram the liver of male mice to self-assemble multiple siRNAs into secretory small extracellular vesicles and facilitate in vivo delivery siRNAs through circulating small extracellular vesicles for the combination therapy of mouse models of ulcerative colitis. Particularly, repeated injection of the multi-targeted genetic circuit designed for simultaneous inhibition of TNF-α, B7-1 and integrin α4 rapidly relieves intestinal inflammation and exerts a synergistic therapeutic effect against ulcerative colitis through suppressing the pro-inflammatory cascade in colonic macrophages, inhibiting the costimulatory signal to T cells and blocking T cell homing to sites of inflammation. More importantly, we design an AAV-driven genetic circuit to induce substantial and lasting inhibition of TNF-α, B7-1 and integrin α4 through only a single injection. Overall, this study establishes a feasible combination therapeutic strategy for ulcerative colitis, which may offer an alternative to conventional biological therapies requiring two or more independent compounds or antibodies. Management of ulcerative colitis can require a combination of treatments targeting different pathways. Here the authors design a therapy for ulcerative colitis based on a multitargeted genetic circuit to simultaneously target TNF-α, B7-1 and integrin α4, and show the therapy is effective in male mice with induced or spontaneous genetic colitis.
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影响因子：
2.4
作者：
Kiourtis C;Wilczynska A;Nixon C;Clark W;May S;Bird TG
通讯作者：
Bird TG
DOI：
10.1126/science.aau6977
发表时间：
2020-02-07
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Kalluri R;LeBleu VS
通讯作者：
LeBleu VS
影响因子：
4.9
作者：
Boschetti, Gilles;Nancey, Stephane;Kaiserlian, Dominique
通讯作者：
Kaiserlian, Dominique
体内自组装小RNA作为新一代RNAi疗法
影响因子：
44.1
作者：
Fu Z;Zhang X;Zhou X;Ur-Rehman U;Yu M;Liang H;Guo H;Guo X;Kong Y;Su Y;Ye Y;Hu X;Cheng W;Wu J;Wang Y;Gu Y;Lu SF;Wu D;Zen K;Li J;Yan C;Zhang CY;Chen X
通讯作者：
Chen X
影响因子：
24.5
作者：
Hueber W;Sands BE;Lewitzky S;Vandemeulebroecke M;Reinisch W;Higgins PD;Wehkamp J;Feagan BG;Yao MD;Karczewski M;Karczewski J;Pezous N;Bek S;Bruin G;Mellgard B;Berger C;Londei M;Bertolino AP;Tougas G;Travis SP;Secukinumab in Crohn's Disease Study Group
通讯作者：
Secukinumab in Crohn's Disease Study Group