Treatment of osteoarthritis using a helper-dependent adenoviral vector retargeted to chondrocytes

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Ruan , M Z C , Cerullo , V , Cela , R , Clarke , C , Lundgren-Akerlund , E , Barry , M A & Lee , B H L 2016 , ' Treatment of osteoarthritis using a helper-dependent adenoviral vector retargeted to chondrocytes ' , Molecular therapy-Methods & clinical development , vol. 3 , 16008 . https://doi.org/10.1038/mtm.2016.8

Title: Treatment of osteoarthritis using a helper-dependent adenoviral vector retargeted to chondrocytes
Author: Ruan, Merry Z. C.; Cerullo, Vincenzo; Cela, Racel; Clarke, Chris; Lundgren-Akerlund, Evy; Barry, Michael A.; Lee, Brendan H. L.
Contributor: University of Helsinki, Faculty of Pharmacy
Date: 2016
Language: eng
Number of pages: 8
Belongs to series: Molecular therapy-Methods & clinical development
ISSN: 2329-0501
URI: http://hdl.handle.net/10138/208499
Abstract: Osteoarthritis (OA) is a joint disease characterized by degeneration of the articular cartilage, subchondral bone remodeling, and secondary inflammation. It is among the top three causes of chronic disability, and currently there are no treatment options to prevent disease progression. The localized nature of OA makes it an ideal candidate for gene and cell therapy. However, gene and cell therapy of OA is impeded by inefficient gene transduction of chondrocytes. In this study, we developed a broadly applicable system that retargets cell surface receptors by conjugating antibodies to the capsid of helper-dependent adenoviral vectors (HDVs). Specifically, we applied this system to retarget chondrocytes by conjugating an HDV to an alpha-10 integrin monoclonal antibody (a10mab). We show that a10mab-conjugated HDV (a10mabHDV)-infected chondrocytes efficiently in vitro and in vivo while detargeting other cell types. The therapeutic index of an intra-articular injection of 10mabHDV-expressing proteoglycan 4 (PRG4) into a murine model of post-traumatic OA was 10-fold higher than with standard HDV. Moreover, we show that PRG4 overexpression from articular, superficial zone chondrocytes is effective for chondroprotection in postinjury OA and that a-10 integrin is an effective protein for chondrocyte targeting.
Subject: MEDIATED GENE-TRANSFER
VIRAL VECTORS
THERAPY
ARTHRITIS
CARTILAGE
LUBRICIN
EXPRESSION
MOUSE
CELLS
3121 General medicine, internal medicine and other clinical medicine
317 Pharmacy
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