Evidence map›Paper›PMID 20374510›Full record

ArticleOral diseases2010

Evaluation of a rapamycin-regulated serotype 2 adeno-associated viral vector in macaque parotid glands.

C Zheng, A Voutetakis, M Metzger, S Afione, A P Cotrim, M A Eckhaus, V M Rivera, T Clackson, J A Chiorini, R E Donahue and 2 more

Abstract readEvaluation Study
In one paragraph

Article in Oral diseases, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed
–field-weighted citation impact, top 93% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 citations in OpenAlex.

  1. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

C ZhengMolecular Physiology and Therapeutics Branch, National Institute of Dental and Craniofacial Research, Bethesda, MD 20892-1190, USA.
A Voutetakis
M Metzger
S Afione
A P Cotrim
M A Eckhaus
V M Rivera
T Clackson
J A Chiorini
R E Donahue
C E Dunbar
B J Baum
National Institute of Dental and Craniofacial Research · USNational Heart Lung and Blood Institute · USAriadne Diagnostics (United States) · USNational Institutes of Health · US

Funding

Adeno-associated Virus Biology And Utilization For Gene TransferZIADE000695 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI CHIORINI, JAY · 2009 to 2025
$36.6M
Retroviral Mediated Gene Transfer Into Primate Hematopoietic CellsZICHL002338 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI DONAHUE, ROBERT E · 2010 to 2018
$30.5M
Optimization of gene transfer safety and efficacy focusing on the NHP modelZIAHL002339 · NHLBI · NATIONAL HEART, LUNG, AND BLOOD INSTITUTE · PI DUNBAR, CYNTHIA E · 2009 to 2025
$26.8M
SALIVARY GLAND SECRETORY MECHANISMS DURING NORMAL AND ALTERED FUNCTIONAL STATESZ01DE000336 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI BAUM, BRUCE J · 1985 to 2008
$7.0M
Salivary Gland Secretion Mechanisms During Normal And Altered Functional StatesZIADE000336 · NIDCR · NATIONAL INSTITUTE OF DENTAL & CRANIOFACIAL RESEARCH · PI BAUM, BRUCE J · 2009 to 2011
$5.9M
Intramural NIH HHS Z01 DE000336
6 · The paper itself

Abstract

objectivesSalivary glands are useful target organs for local and systemic gene therapeutics. For such applications, the regulation of transgene expression is important. Previous studies by us in murine submandibular glands showed that a rapamycin transcriptional regulation system in a single serotype 2, adeno-associated viral (AAV2) vector was effective for this purpose. This study evaluated if such a vector was similarly useful in rhesus macaque parotid glands.

methodsA recombinant AAV2 vector (AAV-TF-RhEpo-2.3w), encoding rhesus erythropoietin (RhEpo) and a rapamycin-inducible promoter, was constructed. The vector was administered to macaques at either of two doses [1.5 x 10(11) (low dose) or 1.5 x 10(12) (high dose) vector genomes] via cannulation of Stensen's duct. Animals were followed up for 12-14 weeks and treated at intervals with rapamycin (0.1 or 0.5 mg kg(-1)) to induce gene expression. Serum chemistry, hematology, and RhEpo levels were measured at interval.

resultsAAV-TF-RhEpo-2.3w administration led to low levels of rapamycin-inducible RhEpo expression in the serum of most macaques. In five animals, no significant changes were seen in serum chemistry and hematology values over the study. One macaque, however, developed pneumonia, became anemic and subsequently required euthanasia. After the onset of anemia, a single administration of rapamycin led to significant RhEpo production in this animal.

conclusionAdministration of AAV-TF-RhEpo-2.3w to macaque parotid glands was generally safe, but led only to low levels of serum RhEpo in healthy animals following rapamycin treatment.

Indexed as

Transduction, GeneticAdenoviridaeAnimalsDose-Response Relationship, DrugErythropoietinGene Expression RegulationGenetic VectorsMacaca mulattaMaleParotid GlandPromoter Regions, GeneticRecombinant ProteinsSirolimusTransgenesErythropoietinRecombinant ProteinsSirolimus

Identifiers

PMID20374510
PMCPMC2852890
OpenAlexW1972873228

What OpenQuestion holds

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Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.