Evidence map›Paper›PMID 30393908›Full record

ArticleThe journal of gene medicine2018

Enhancing atrial-specific gene expression using a calsequestrin cis-regulatory module 4 with a sarcolipin promoter.

Jimeen Yoo, Erik Kohlbrenner, Okkil Kim, Roger J Hajjar, Dongtak Jeong

Open access · hybridAbstract read
In one paragraph

Article in The journal of gene medicine, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.7field-weighted citation impact, top 23% 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

7 citing papers in PubMed, 13 citations in OpenAlex.

  1. Gene therapy for atrial fibrillation.Journal of molecular and cellular cardiology · 2024
    Review
  2. Review
  3. Article
  4. Article
  5. Identification of the Core Pollen-Specific Regulation in the RiceInternational journal of molecular sciences · 2020
    Article
  6. Hepatitis B Virus X Protein-Induced RORBioMed research international · 2019
    Article
  7. 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

5 authors at 1 institution in 1 country.

Jimeen YooCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Erik KohlbrennerCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Okkil KimCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Roger J HajjarCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Dongtak JeongCardiovascular Research Center, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Icahn School of Medicine at Mount Sinai · US

Funding

TRIP: Targeted Gene Therapy for the Treatment of Heart FailureP50HL112324 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI ASCHEIM, DEBORAH DAVIS, HAJJAR, ROGER J. · 2012 to 2014
$6.4M
Therapeutic Mechanisms of Cardiac Progenitors in Ischemic CardiomyopathyR01HL135093 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI FISH, KENNETH MICHAEL, KOVACIC, JASON CIRIL · 2017 to 2020
$3.4M
SUMO1 and SERCA2a FunctionR01HL117505 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WEBER, THOMAS · 2013 to 2020
$3.4M
Anti-AAV Antibodies as an Obstacle to Cardiac AAV Gene TherapyR01HL131404 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI WEBER, THOMAS · 2016 to 2019
$3.3M
Calcium Pump Activators for Heart Failure TherapyR01HL129814 · NHLBI · UNIVERSITY OF MINNESOTA · PI THOMAS, DAVID D · 2015 to 2018
$3.2M
Targeting Abnormal Calcium Cycling Using Novel Gene Therapy VectorsR01HL119046 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI AKAR, FADI GABRIEL, HAJJAR, ROGER J. · 2014 to 2017
$2.9M
Role of miR25 in Heart FailureR01HL128072 · NHLBI · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI HAJJAR, ROGER J., MERCOLA, MARK · 2015 to 2018
$2.5M
Foundation for the National Institutes of Health P50HL112324Foundation for the National Institutes of Health R01HL117505Foundation for the National Institutes of Health R01HL 119046Foundation for the National Institutes of Health R01HL128072Foundation for the National Institutes of Health R01HL129814Foundation for the National Institutes of Health R01HL131404Foundation for the National Institutes of Health R01HL135093NHLBI NIH HHS P50 HL112324NHLBI NIH HHS R01 HL117505NHLBI NIH HHS R01 HL119046NHLBI NIH HHS R01 HL128072NHLBI NIH HHS R01 HL129814NHLBI NIH HHS R01 HL131404NHLBI NIH HHS R01 HL135093
6 · The paper itself

Abstract

backgroundCardiac gene therapy using the adeno-associated virus serotype 9 vector is widely used because of its efficient transduction. However, the promoters used to drive expression often cause off-target localization. To overcome this, studies have applied cardiac-specific promoters, although expression is debilitated compared to that of ubiquitous promoters. To address these issues in the context of atrial-specific gene expression, an enhancer calsequestrin cis-regulatory module 4 (CRM4) and the highly atrial-specific promoter sarcolipin were combined to enhance expression and minimize off tissue expression.

methodsTo observe expression and bio-distribution, constructs were generated using two different reporter genes: luciferase and enhanced green fluorescent protein (EGFP). The ubiquitous cytomegalovirus (CMV), sarcolipin (SLN) and CRM4 combined with sarcolipin (CRM4.SLN) were compared and analyzed using the luciferase assay, western blotting, a quantitative polymerase chain reaction and fluorescence imaging.

resultsThe CMV promoter containing vectors showed the strongest expression in vitro and in vivo. However, the module SLN combination showed enhanced atrial expression and a minimized off-target effect even when compared with the individual SLN promoter.

conclusionsFor gene therapy involving atrial gene transfer, the CRM4.SLN combination is a promising alternative to the use of the CMV promoter. CRM4.SLN had significant atrial expression and minimized extra-atrial expression.

Indexed as

Gene Expression RegulationAnimalsCalsequestrinCytomegalovirusDependovirusGenetic TherapyGenetic VectorsGreen Fluorescent ProteinsHeart AtriaHeart FailureHumansLuciferasesMiceMuscle ProteinsPromoter Regions, GeneticProteolipidsCalsequestrinenhanced green fluorescent proteinGreen Fluorescent ProteinsLuciferasesMuscle ProteinsProteolipidssarcolipinAAV9atriumcis-acting regulatory moduleCRM4gene therapysarcolipin

Identifiers

PMID30393908
PMCPMC6519042
OpenAlexW2899957857

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.