Identification of liver-specific enhancer – promoter activity in the 3 ′ untranslated region of the wild-type AAV2 genome
Nature Genetics 49, 1267 (2017).
doi:10.1038/ng.3893
Authors: Grant J Logan, Allison P Dane, Claus V Hallwirth, Christine M Smyth, Emilie E Wilkie, Anais K Amaya, Erhua Zhu, Neeta Khandekar, Samantha L Ginn, Sophia H Y Liao, Sharon C Cunningham, Natsuki Sasaki, Martí Cabanes-Creus, Patrick P L Tam, David W Russell, Leszek Lisowski & Ian E Alexander
Vectors based on adeno-associated virus type 2 (AAV2) are powerful tools for gene transfer and genome editing applications. The level of interest in this system has recently surged in response to reports of therapeutic efficacy in human clinical trials, most notably for those in patients with hemophilia B (ref. 3). Understandably, a recent report drawing an association between AAV2 integration events and human hepatocellular carcinoma (HCC) has generated controversy about the causal or incidental nature of this association and the implications for AAV vector safety. Here we describe and functionally characterize a previously unknown liver-specific enhancer–promoter element in the wild-type AAV2 genome that is found between the stop codon of the cap gene, which encodes proteins that form the capsid, and the right-hand inverted terminal repeat. This 124-nt sequence is within the 163-nt common insertion region of the AAV genome, which has been implicated in the dysregulation of known HCC driver genes and thus offers added insight into the possible link between AAV integration events and the multifactorial pathog...
Source: Nature Genetics - Category: Genetics & Stem Cells Authors: Grant J Logan Allison P Dane Claus V Hallwirth Christine M Smyth Emilie E Wilkie Anais K Amaya Erhua Zhu Neeta Khandekar Samantha L Ginn Sophia H Y Liao Sharon C Cunningham Natsuki Sasaki Mart í Cabanes-Creus Patrick P L Tam David W Russell Leszek Lisow Tags: Letter Source Type: research
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