Abstract:
:In vivo imaging of vector transgene expression would be particularly valuable for repetitive monitoring of therapy in the brain, where invasive tissue sampling is contraindicated. We evaluated adeno-associated virus vector expression of a dopamine-2 receptor (D2R) mutant (D2R80A) by positron emission tomography in the brains of mice and cats. D2R80A is inactivated for intracellular signaling and binds subphysiologic amounts of the radioactive [(18)F]-fallypride analog of dopamine. The [(18)F]-fallypride signal bound to D2R80A in the injection site was normalized to the signal from endogenous D2R in the striatum and showed stable levels of expression within individual animals. A separate adeno-associated virus type 1 vector with identical gene expression control elements, expressing green fluorescent protein or a therapeutic gene, was coinjected with the D2R80A vector at equal doses into specific sites. Both transgenes had similar levels of gene expression by immunohistochemistry, in situ hybridization, and quantitative PCR assays, demonstrating that D2R80A is a faithful surrogate measure for expression of a gene of interest. This dual vector approach allows the D2R80A gene to be used with any therapeutic gene and to be injected into a single site for monitoring while the therapeutic gene can be distributed more widely as needed in each disease.
journal_name
Mol Ther Methods Clin Devjournal_title
Molecular therapy. Methods & clinical developmentauthors
Yoon SY,Gay-Antaki C,Ponde DE,Poptani H,Vite CH,Wolfe JHdoi
10.1038/mtm.2014.16subject
Has Abstractpub_date
2014-06-04 00:00:00pages
14016issn
2329-0501pii
S2329-0501(16)30081-Xjournal_volume
1pub_type
杂志文章abstract::Adeno-associated virus (AAV) vectors have emerged as a safe and efficient gene therapy platform. One complication is that a significant amount of empty particles have always been generated as impurities during AAV vector production. However, the effects of such particles on AAV vector performance remain unclear. Here ...
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
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abstract::Surfactant protein B (SPB) deficiency is a severe monogenic interstitial lung disorder that leads to loss of life in infants as a result of alveolar collapse and respiratory distress syndrome. The development and assessment of curative therapies for the deficiency are limited by the general lack of well-characterized ...
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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
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journal_title:Molecular therapy. Methods & clinical development
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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
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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
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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
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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
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journal_title:Molecular therapy. Methods & clinical development
pub_type: 杂志文章
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