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DOI | 10.1038/s41467-017-02246-0 |
High levels of AAV vector integration into CRISPR-induced DNA breaks | |
Hanlon, Killian S.1,2; Kleinstiver, Benjamin P.3,4,5; Garcia, Sara P.5,6,7; Zaborowski, Mikolaj P.2,8,9; Volak, Adrienn2,10; Spirig, Stefan E.10; Muller, Alissa10; Sousa, Alexander A.6,7; Tsai, Shengdar Q.11; Bengtsson, Niclas E.12; Loov, Camilla13; Ingelsson, Martin13; Chamberlain, Jeffrey S.12; Corey, David P.1; Aryee, Martin J.5,6,7,14; Joung, J. Keith5,6,7; Breakefield, Xandra O.2,8; Maguire, Casey A.2,8; Gyorgy, Bence1,2,10 | |
2019-09-30 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2019 |
卷号 | 10 |
文章类型 | Article |
语种 | 英语 |
国家 | USA; Poland; Switzerland; Sweden |
英文摘要 | Adeno-associated virus (AAV) vectors have shown promising results in preclinical models, but the genomic consequences of transduction with AAV vectors encoding CRISPR-Cas nucleases is still being examined. In this study, we observe high levels of AAV integration (up to 47%) into Cas9-induced double-strand breaks (DSBs) in therapeutically relevant genes in cultured murine neurons, mouse brain, muscle and cochlea. Genome-wide AAV mapping in mouse brain shows no overall increase of AAV integration except at the CRISPR/Cas9 target site. To allow detailed characterization of integration events we engineer a miniature AAV encoding a 465 bp lambda bacteriophage DNA (AAV-lambda 465), enabling sequencing of the entire integrated vector genome. The integration profile of AAV-465 lambda in cultured cells display both full-length and fragmented AAV genomes at Cas9 on-target sites. Our data indicate that AAV integration should be recognized as a common outcome for applications that utilize AAV for genome editing. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000488235000009 |
WOS关键词 | ADENOASSOCIATED VIRUS VECTORS ; MOUSE MODEL ; HEPATIC GENOTOXICITY ; THERAPEUTIC APPROACH ; HEARING-LOSS ; GENOMES ; NUCLEASES ; DOMINANT ; DELIVERY ; MUSCLE |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203598 |
专题 | 资源环境科学 |
作者单位 | 1.Harvard Med Sch, Dept Neurobiol, Boston, MA 02115 USA; 2.Massachusetts Gen Hosp, Dept Neurol, Mol Neurogenet Unit, Charlestown, MA 02129 USA; 3.Massachusetts Gen Hosp, Ctr Genom Med, Boston, MA 02114 USA; 4.Massachusetts Gen Hosp, Dept Pathol, Boston, MA 02114 USA; 5.Harvard Med Sch, Dept Pathol, Boston, MA 02115 USA; 6.Massachusetts Gen Hosp, Mol Pathol Unit, Charlestown, MA 02129 USA; 7.Massachusetts Gen Hosp, Ctr Canc Res & Ctr Computat & Integrat Biol, Charlestown, MA USA; 8.Harvard Med Sch, Program Neurosci, Boston, MA 02115 USA; 9.Poznan Univ Med Sci, Dept Gynecol Obstet & Gynecol Oncol, Div Gynecol Oncol, PL-60535 Poznan, Poland; 10.Inst Mol & Clin Ophthalmol Basel, CH-4031 Basel, Switzerland; 11.St Jude Childrens Res Hosp, Dept Hematol, 332 N Lauderdale St, Memphis, TN 38105 USA; 12.Univ Washington, Dept Neurol, Seattle, WA 98195 USA; 13.Uppsala Univ, Dept Publ Hlth & Caring Sci, Geriatr, Uppsala, Sweden; 14.Harvard TH Chan Sch Publ Hlth, Dept Biostat, Boston, MA USA |
推荐引用方式 GB/T 7714 | Hanlon, Killian S.,Kleinstiver, Benjamin P.,Garcia, Sara P.,et al. High levels of AAV vector integration into CRISPR-induced DNA breaks[J]. NATURE COMMUNICATIONS,2019,10. |
APA | Hanlon, Killian S..,Kleinstiver, Benjamin P..,Garcia, Sara P..,Zaborowski, Mikolaj P..,Volak, Adrienn.,...&Gyorgy, Bence.(2019).High levels of AAV vector integration into CRISPR-induced DNA breaks.NATURE COMMUNICATIONS,10. |
MLA | Hanlon, Killian S.,et al."High levels of AAV vector integration into CRISPR-induced DNA breaks".NATURE COMMUNICATIONS 10(2019). |
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