本期Nature Communications上發(fā)表的一篇論文報告說,，患有出血性疾病“A型血友病”的狗采用基因療法成功得到了治療。這項研究（在其中患病的狗被發(fā)現(xiàn)2.5年時間沒有發(fā)生嚴(yán)重出血）是第一次采用以血細(xì)胞為目標(biāo)的基因療法在一個大型動物模型中演示“A型血友病”的治療,，代表著朝在臨床上對嚴(yán)重“A型血友病”人類患者采用這種療法的方向上邁進(jìn)了一步,。
“A型血友病”（與凝血蛋白“因子VIII”缺乏相關(guān)的一種遺傳性出血疾病）影響萬分之一的人,。David Wilcox及同事利用一種病毒將一個功能性“因子VIII”基因引入到患有“A型血友病”的狗的“外周血干細(xì)胞”內(nèi),。這種基因療法（該研究小組在三只狗身上對這種療法的不同形式進(jìn)行了測試）導(dǎo)致 “因子VIII”在血小板中的生成和存儲，而這以前在這些動物身上是不可能發(fā)生的,。作者報告說,，在接受基因療法后產(chǎn)生最高水平“因子VIII”的兩只狗在整個2.5年的隨訪期沒有發(fā)生過嚴(yán)重出血。三只實驗狗（在基因療法后接受免疫抑制劑用藥長達(dá)90天）中沒有一只產(chǎn)生針對“因子VIII”的抗體,，而如果有這種抗體的話會影響治療效果,。（生物谷Bioon.com）
生物谷推薦的英文摘要
Nature Communications doi:10.1038/ncomms3773
Platelet-targeted gene therapy with human factor VIII establishes haemostasis in dogs with haemophilia A
Lily M. Du，Paquita Nurden,，Alan T. Nurden,，Timothy C. Nichols，Dwight A. Bellinger,，Eric S. Jensen,，Sandra L. Haberichter，Elizabeth Merricks,，Robin A. Raymer,，Juan Fang，Sevasti B. Koukouritaki,，Paula M. Jacobi,，Troy B. Hawkins，Kenneth Cornetta，Qizhen Shi& David A. Wilcox
It is essential to improve therapies for controlling excessive bleeding in patients with haemorrhagic disorders. As activated blood platelets mediate the primary response to vascular injury,， we hypothesize that storage of coagulation Factor VIII within platelets may provide a locally inducible treatment to maintain haemostasis for haemophilia A. Here we show that haematopoietic stem cell gene therapy can prevent the occurrence of severe bleeding episodes in dogs with haemophilia A for at least 2.5 years after transplantation. We employ a clinically relevant strategy based on a lentiviral vector encoding the ITGA2B gene promoter,， which drives platelet-specific expression of human FVIII permitting storage and release of FVIII from activated platelets. One animal receives a hybrid molecule of FVIII fused to the von Willebrand Factor propeptide-D2 domain that traffics FVIII more effectively into α-granules. The absence of inhibitory antibodies to platelet-derived FVIII indicates that this approach may have benefit in patients who reject FVIII replacement therapies. Thus， platelet FVIII may provide effective long-term control of bleeding in patients with haemophilia A.
