ArticleJournal of cardiac failure2011
A pharmacokinetic analysis of molecular cardiac surgery with recirculation mediated delivery of βARKct gene therapy: developing a quantitative definition of the therapeutic window.
Article in Journal of cardiac failure, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Small non-coding RNA therapeutics for cardiovascular disease.European heart journal · 2022Review
- Targeted delivery of therapeutic agents to the heart.Nature reviews. Cardiology · 2021Review
- Site-Specific Glycation and Chemo-enzymatic Antibody Sortagging for the Retargeting of rAAV6 to Inflamed Endothelium.Molecular therapy. Methods & clinical development · 2019Article
- Liquid jet delivery method featuring S100A1 gene therapy in the rodent model following acute myocardial infarction.Gene therapy · 2016Article
- Gene delivery technologies for cardiac applications.Gene therapy · 2012Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTwo major problems for translating gene therapy for heart failure therapy are: safe and efficient delivery and the inability to establish a relationship between vector exposure and in vivo effects. We present a pharmacokinetics (PK) analysis of molecular cardiac surgery with recirculating delivery (MCARD) of scAAV6-βARKct. MCARD's stable cardiac specific delivery profile was exploited to determine vector exposure, half-life, and systemic clearance. METHODS AND
resultsFive naive sheep underwent MCARD with 10(14) genome copies of scAAV6-βARKct. Blood samples were collected over the recirculation interval time of 20 minutes and evaluated with quantitative polymerase chain reaction (qPCR). C(t) curves were generated and expressed on a log scale. The exposure, half-life, and clearance curves were generated for analysis. qPCR and Western blots were used to determine biodistribution. Finally, all in vivo transduction data was plotted against MCARD's PK to determine if a relationship existed. Vector concentrations at each time point were (cardiac and systemic, respectively): 5 minutes: 9.16 ± 0.15 and 3.21 ± 0.38; 10 minutes: 8.81 ± 0.19 and 3.62 ± 0.37; 15 minutes: 8.75 ± 0.12 and 3.69 ± 0.31; and 20 minutes: 8.66 ± 0.22 and 3.95 ± 0.26; P < .00001. The half life of the vector was 2.66 ± 0.24 minutes. PK model data revealed that only 0.61 ± 0.43% of the original dose remained in the blood after delivery, and complete clearance from the system was achieved at 1 week. A PK transfer function revealed a positive correlation between exposure and in vivo transduction. Robust βARKct expression was found in all cardiac regions with none in the liver.
conclusionMCARD may offer a viable method to establish a relationship between vector exposure and in vivo transduction. Using this methodology, it may be possible to address a critical need for establishing an effective therapeutic window.
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