Assembly and Functional Analysis of an S/MAR Based Episome with the Cystic Fibrosis Transmembrane Conductance Regulator Gene.
Assembly and Functional Analysis of an S/MAR Based Episome with the Cystic Fibrosis Transmembrane Conductance Regulator Gene.
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DOI：
10.3390/ijms19041220
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发表时间：
2018-04-17
影响因子：
5.6
通讯作者：
Ascenzioni F
中科院分区：
文献类型：
--
作者：
De Rocco D;Pompili B;Castellani S;Morini E;Cavinato L;Cimino G;Mariggiò MA;Guarnieri S;Conese M;Del Porto P;Ascenzioni F
Improving the efficacy of gene therapy vectors is still an important goal toward the development of safe and efficient gene therapy treatments. S/MAR (scaffold/matrix attached region)-based vectors are maintained extra-chromosomally in numerous cell types, which is similar to viral-based vectors. Additionally, when established as an episome, they show a very high mitotic stability. In the present study we tested the idea that addition of an S/MAR element to a CFTR (cystic fibrosis transmembrane conductance regulator) expression vector, may allow the establishment of a CFTR episome in bronchial epithelial cells. Starting from the observation that the S/MAR vector pEPI-EGFP (enhanced green fluorescence protein) is maintained as an episome in human bronchial epithelial cells, we assembled the CFTR vector pBQ-S/MAR. This vector, transfected in bronchial epithelial cells with mutated CFTR, supported long term wt CFTR expression and activity, which in turn positively impacted on the assembly of tight junctions in polarized epithelial cells. Additionally, the recovery of intact pBQ-S/MAR, but not the parental vector lacking the S/MAR element, from transfected cells after extensive proliferation, strongly suggested that pBQ-S/MAR was established as an episome. These results add a new element, the S/MAR, that can be considered to improve the persistence and safety of gene therapy vectors for cystic fibrosis pulmonary disease.
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影响因子：
10
作者：
Gill, Deborah R.;Hyde, Stephen C.
通讯作者：
Hyde, Stephen C.
DOI：
10.1126/science.1255825
发表时间：
2014-08-15
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Hoegger MJ;Fischer AJ;McMenimen JD;Ostedgaard LS;Tucker AJ;Awadalla MA;Moninger TO;Michalski AS;Hoffman EA;Zabner J;Stoltz DA;Welsh MJ
通讯作者：
Welsh MJ
影响因子：
76.2
作者：
Elborn, J. Stuart;Ramsey, Bonnie W.;Wainwright, Claire E.
通讯作者：
Wainwright, Claire E.
影响因子：
3.7
作者：
Cifani N;Pompili B;Anile M;Patella M;Diso D;Venuta F;Cimino G;Quattrucci S;Di Domenico EG;Ascenzioni F;Del Porto P
通讯作者：
Del Porto P
影响因子：
5.1
作者：
Auriche, C.;Di Domenico, E. G.;Ascenzioni, F.
通讯作者：
Ascenzioni, F.