Tropism of engineered and evolved recombinant AAV serotypes in the rd1 mouse and ex vivo primate retina.
Tropism of engineered and evolved recombinant AAV serotypes in the rd1 mouse and ex vivo primate retina.
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DOI：
10.1038/gt.2017.85
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发表时间：
2017-12
期刊：
影响因子：
5.1
通讯作者：
MacLaren RE
中科院分区：
文献类型：
--
作者：
Hickey DG;Edwards TL;Barnard AR;Singh MS;de Silva SR;McClements ME;Flannery JG;Hankins MW;MacLaren RE
关于腺相关病毒（AAV）的血清型最适合针对特定的视网膜细胞类型和手术递送途径是玻璃体内还是视网膜下，存在很多争论。这项研究比较了迄今为止已知的三种最有效的AAV载体在视网膜变性小鼠模型（rd1小鼠）和猕猴和人类视网膜外植体中的作用。绿色荧光蛋白（GFP）由无所不在的启动子驱动，被包装成三种AAV衣壳：AAV2/8(Y733F), AAV2/2（quad Y-F）和AAV2/2（7m8）。总体而言，AAV2/2（7m8）转导视网膜面积最大，导致GFP表达水平最高，其次是AAV2/2（quad Y-F）和AAV2/8（Y733F）。AAV2/2（7m8）和AAV2/2（quad Y-F）无论在玻璃体内注射还是在视网膜下注射，其转导模式都相似。与视网膜下注射相比，AAV2/8（Y733F）在玻璃体内注射时对视网膜的转导面积明显更小。在小鼠视网膜中，视网膜神经节细胞、水平细胞和视网膜色素上皮表达较高水平的GFP，而无突细胞表达较低水平的GFP，双极细胞很少被转导。视锥细胞是猕猴视网膜外植体中最常见的转导细胞类型，而人视网膜外植体中最主要的转导细胞类型是椎体细胞。在测试的AAV血清型中，AAV2/2（7m8）在变性小鼠视网膜、猕猴和人视网膜外植体中转导一系列细胞类型最有效。
There is much debate on the adeno-associated virus (AAV) serotype that best targets specific retinal cell types and the route of surgical delivery—intravitreal or subretinal. This study compared three of the most efficacious AAV vectors known to date in a mouse model of retinal degeneration (rd1 mouse) and macaque and human retinal explants. Green fluorescent protein (GFP) driven by a ubiquitous promoter was packaged into three AAV capsids: AAV2/8(Y733F), AAV2/2(quad Y-F) and AAV2/2(7m8). Overall, AAV2/2(7m8) transduced the largest area of retina and resulted in the highest level of GFP expression, followed by AAV2/2(quad Y-F) and AAV2/8(Y733F). AAV2/2(7m8) and AAV2/2(quad Y-F) both resulted in similar patterns of transduction whether they were injected intravitreally or subretinally. AAV2/8(Y733F) transduced a significantly smaller area of retina when injected intravitreally compared with subretinally. Retinal ganglion cells, horizontal cells and retinal pigment epithelium expressed relatively high levels of GFP in the mouse retina, whereas amacrine cells expressed low levels of GFP and bipolar cells were infrequently transduced. Cone cells were the most frequently transduced cell type in macaque retina explants, whereas Müller cells were the predominant transduced cell type in human retinal explants. Of the AAV serotypes tested, AAV2/2(7m8) was the most effective at transducing a range of cell types in degenerate mouse retina and macaque and human retinal explants.
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影响因子：
4.1
作者：
MacLaren, RE
通讯作者：
MacLaren, RE
影响因子：
--
作者：
Jacobson, Samuel G.;Cideciyan, Artur V.;Ratnakaram, Ramakrishna;Heon, Elise;Schwartz, Sharon B.;Roman, Alejandro J.;Peden, Marc C.;Aleman, Tomas S.;Boye, Sanford L.;Sumaroka, Alexander;Conlon, Thomas J.;Calcedo, Roberto;Pang, Ji-Jing;Erger, Kirsten E.;Olivares, Melani B.;Mullins, Cristina L.;Swider, Malgorzata;Kaushal, Shalesh;Feuer, William J.;Iannaccone, Alessandro;Fishman, Gerald A.;Stone, Edwin M.;Byrne, Barry J.;Hauswirth, William W.
通讯作者：
Hauswirth, William W.
影响因子：
11.1
作者：
Cronin T;Vandenberghe LH;Hantz P;Juttner J;Reimann A;Kacsó AE;Huckfeldt RM;Busskamp V;Kohler H;Lagali PS;Roska B;Bennett J
通讯作者：
Bennett J
影响因子：
16.6
作者：
Nishiguchi, Koji M.;Carvalho, Livia S.;Rizzi, Matteo;Powell, Kate;Holthaus, Sophia-Martha Kleine;Azam, Selina A.;Duran, Yanai;Ribeiro, Joana;Luhmann, Ulrich F. O.;Bainbridge, James W. B.;Smith, Alexander J.;Ali, Robin R.
通讯作者：
Ali, Robin R.
影响因子：
12.4
作者：
Dalkara, Deniz;Kolstad, Kathleen D.;Flannery, John G.
通讯作者：
Flannery, John G.