In vivo retrovirus-mediated gene transfer to the liver of dogs results in transient expression and induction of a cytotoxic immune response.
In vivo retrovirus-mediated gene transfer to the liver of dogs results in transient expression and induction of a cytotoxic immune response.
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体内逆转录病毒介导的基因转移至狗的肝脏，导致瞬时表达并诱导细胞毒性免疫反应。
作者：
A. Izembart;E. Aguado;O. Gauthier;D. Aubert;P. Moullier;N. Ferry
研究了使用携带大肠杆菌β-半乳糖苷酶基因的高滴度重组逆转录病毒载体在再生狗肝脏中的基因转移。部分肝切除后，将含有双嗜性或长臂猿假型重组逆转录病毒的上清液注入比格犬的外周静脉中。测定动物的肝再生动力学，并在再生期间每天进行输注，持续 4 或 5 天。手术结束时，高达 2.8% 的肝细胞 β-半乳糖苷酶呈阳性。但3周后阳性细胞数量迅速下降，几乎没有检测到阳性肝细胞。 PCR证明原病毒消失。组织学上，在转导的肝脏中观察到炎症病变。最后，我们证明存在针对表达β-半乳糖苷酶的细胞的细胞毒性T淋巴细胞免疫反应，这可以解释转基因的消失。这项工作表明，使用直接注入循环系统的高滴度逆转录病毒载体进行体内基因传递的效率可能会受到针对感染细胞的细胞毒性免疫反应的阻碍。
Gene transfer in regenerating dog liver using high-titer recombinant retroviral vectors carrying the E. coli beta-galactosidase gene was studied. Supernatants containing amphotropic or gibbon ape pseudotyped recombinant retroviruses were infused into a peripheral vein in beagle dogs after partial hepatectomy. The kinetics of liver regeneration were determined in the animals and daily infusions were carried out for 4 or 5 days during the regeneration period. Up to 2.8% of hepatocytes were beta-galactosidase positive at the end of the procedure. However, the number of positive cells declined rapidly and few positive hepatocytes were detected after 3 weeks. PCR demonstrated the disappearance of the provirus. Histologically, inflammatory lesions were observed in the transduced livers. Finally, we demonstrated the presence of a cytotoxic T lymphocyte immune response directed against beta-galactosidase-expressing cells, which could explain the disappearance of the transgene. This work suggests that the efficiency of in vivo gene delivery using high-titer retroviral vectors directly infused into the circulation may be hampered by a cytotoxic immune response against the infected cells.
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影响因子：
56.9
作者：
KAY, MA;ROTHENBERG, S;WOO, SLC
通讯作者：
WOO, SLC
腺病毒介导的双嗜性逆转录病毒受体 cDNA 的转移可增加培养细胞中的逆转录病毒转导。
DOI：
10.1089/hum.1995.6.1-5
发表时间：
1995
期刊：
Human gene therapy.
影响因子：
--
作者：
Lieber,A;VranckenPeeters,MJ;Kay,MA
通讯作者：
Kay,MA
腺病毒介导的尿激酶基因转移诱导肝再生，并允许体内肝细胞有效的逆转录病毒转导。
DOI：
10.1073/pnas.92.13.6210
发表时间：
1995
影响因子：
11.1
作者：
Lieber,A;VranckenPeeters,MJ;Meuse,L;Fausto,N;Perkins,J;Kay,MA
通讯作者：
Kay,MA
通过体内逆转录病毒基因转移长期降低 Gunn 大鼠血清胆红素水平。
DOI：
10.1002/lt.500040111
发表时间：
1998
期刊：
Liver transplantation and surgery : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society
影响因子：
--
作者：
Tada,K;Chowdhury,NR;Neufeld,D;Bosma,PJ;Heard,M;Prasad,VR;Chowdhury,JR
通讯作者：
Chowdhury,JR
体内腺病毒介导的小鼠肝细胞转基因表达的菌株相关变异：免疫活性和免疫缺陷近交菌株之间的比较。
DOI：
--
发表时间：
1995
期刊：
Gene therapy.
影响因子：
--
作者：
Barr,D;Tubb,J;Ferguson,D;Scaria,A;Lieber,A;Wilson,C;Perkins,J;Kay,MA
通讯作者：
Kay,MA