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.
journal_name
Mol Ther Methods Clin Devjournal_title
Molecular therapy. Methods & clinical developmentauthors
Ruan MZ,Cerullo V,Cela R,Clarke C,Lundgren-Akerlund E,Barry MA,Lee BHdoi
10.1038/mtm.2016.8subject
Has Abstractpub_date
2016-03-09 00:00:00pages
16008issn
2329-0501pii
S2329-0501(16)30186-3journal_volume
3pub_type
杂志文章abstract::Adeno-associated viruses (AAVs) are the vector of choice for gene therapy in the eye, and self-complementary AAVs (scAAVs), which do not require second-strand DNA synthesis, can be transduced into cells of the trabecular meshwork (TM). The scAAV transduction patterns in the anterior segment of normotensive eyes have b...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.06.009
更新日期:2019-07-10 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
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abstract::Recombinant adeno-associated virus (rAAV)rh74.MCK.GALGT2 is a muscle-specific gene therapy that is being developed to treat forms of muscular dystrophy. Here we report on an isolated limb infusion technique in a non-human primate model, where hindlimb blood flow is transiently isolated using balloon catheters to conce...
journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章,评审
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journal_title:Molecular therapy. Methods & clinical development
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.08.002
更新日期:2018-08-08 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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更新日期:2018-12-05 00:00:00
abstract::rAAVrh74.MCK.GALGT2 is a surrogate gene therapy that inhibits muscular dystrophy in multiple animal models. Here, we report on a dose-response study of functional muscle GALGT2 expression as well as toxicity and biodistribution studies after systemic intravenous (i.v.) delivery of rAAVrh74.MCK.GALGT2. A dose of 4.3 × ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.10.005
更新日期:2019-10-21 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.10.009
更新日期:2020-10-20 00:00:00
abstract::Human immunodeficiency virus (HIV) is an attractive target for chimeric antigen receptor (CAR) therapy. CAR T cells have proved remarkably potent in targeted killing of cancer cells, and we surmised that CAR T cells could prove useful in eradicating HIV-infected cells. Toward this goal, we interrogate several neutrali...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.09.014
更新日期:2020-09-28 00:00:00
abstract::Preclinical studies have demonstrated that a single injection of an adeno-associated virus (AAV) vector into the cerebrospinal fluid (CSF) can achieve widespread gene transfer throughout the central nervous system. Successfully translating this approach to humans requires identifying factors that influence AAV distrib...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.04.012
更新日期:2020-04-18 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2017.08.007
更新日期:2017-09-07 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2015.9
更新日期:2015-03-25 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.57
更新日期:2016-08-24 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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更新日期:2020-05-04 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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更新日期:2020-05-22 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2016.9
更新日期:2016-03-02 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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更新日期:2020-09-16 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2018.01.007
更新日期:2018-01-31 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.08.013
更新日期:2019-09-06 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2019.12.002
更新日期:2019-12-14 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1038/mtm.2014.3
更新日期:2014-03-12 00:00:00
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
doi:10.1016/j.omtm.2020.03.017
更新日期:2020-03-29 00:00:00
abstract::[This corrects the article DOI: 10.1038/mtm.2015.16.]. ...
journal_title:Molecular therapy. Methods & clinical development
pub_type: 已发布勘误
doi:10.1038/mtm.2016.32
更新日期:2016-05-25 00:00:00