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

Merry Z C Ruan, Vincenzo Cerullo, Racel Cela, Chris Clarke, Evy Lundgren-Akerlund, Michael A Barry, Brendan H L Lee

Research output: Contribution to journalArticle

8 Citations (Scopus)

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 α-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 α-10 integrin is an effective protein for chondrocyte targeting.

Original languageEnglish (US)
Article number16008
JournalMolecular Therapy - Methods and Clinical Development
Volume3
DOIs
StatePublished - Mar 16 2016

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Chondrocytes
Osteoarthritis
Integrins
Proteoglycans
Cell- and Tissue-Based Therapy
Genetic Therapy
Monoclonal Antibodies
Therapeutics
Intra-Articular Injections
Joint Diseases
Bone Remodeling
Capsid
Cell Surface Receptors
Articular Cartilage
Protein Transport
Disease Progression
Joints
Inflammation
Antibodies
Genes

ASJC Scopus subject areas

  • Genetics
  • Molecular Biology
  • Molecular Medicine

Cite this

Treatment of osteoarthritis using a helper-dependent adenoviral vector retargeted to chondrocytes. / Ruan, Merry Z C; Cerullo, Vincenzo; Cela, Racel; Clarke, Chris; Lundgren-Akerlund, Evy; Barry, Michael A; Lee, Brendan H L.

In: Molecular Therapy - Methods and Clinical Development, Vol. 3, 16008, 16.03.2016.

Research output: Contribution to journalArticle

Ruan, Merry Z C ; Cerullo, Vincenzo ; Cela, Racel ; Clarke, Chris ; Lundgren-Akerlund, Evy ; Barry, Michael A ; Lee, Brendan H L. / Treatment of osteoarthritis using a helper-dependent adenoviral vector retargeted to chondrocytes. In: Molecular Therapy - Methods and Clinical Development. 2016 ; Vol. 3.
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