Nature Communications (May 2022)
Blocking phospholamban with VHH intrabodies enhances contractility and relaxation in heart failure
- Erwin De Genst,
- Kylie S. Foo,
- Yao Xiao,
- Eduarde Rohner,
- Emma de Vries,
- Jesper Sohlmér,
- Nevin Witman,
- Alejandro Hidalgo,
- Terje R. S. Kolstad,
- William E. Louch,
- Susanne Pehrsson,
- Andrew Park,
- Yasuhiro Ikeda,
- Xidan Li,
- Lorenz M. Mayr,
- Kate Wickson,
- Karin Jennbacken,
- Kenny Hansson,
- Regina Fritsche-Danielson,
- James Hunt,
- Kenneth R. Chien
Affiliations
- Erwin De Genst
- Discovery Sciences, R&D, AstraZeneca
- Kylie S. Foo
- Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Department of Medicine, Karolinska Institutet
- Yao Xiao
- Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Department of Medicine, Karolinska Institutet
- Eduarde Rohner
- Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Department of Medicine, Karolinska Institutet
- Emma de Vries
- Discovery Sciences, R&D, AstraZeneca
- Jesper Sohlmér
- Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Department of Medicine, Karolinska Institutet
- Nevin Witman
- Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Department of Medicine, Karolinska Institutet
- Alejandro Hidalgo
- Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Department of Medicine, Karolinska Institutet
- Terje R. S. Kolstad
- Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo
- William E. Louch
- Institute for Experimental Medical Research, Oslo University Hospital and University of Oslo
- Susanne Pehrsson
- Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca
- Andrew Park
- Biologics Engineering, R&D, AstraZeneca
- Yasuhiro Ikeda
- Biologics Engineering, R&D, AstraZeneca
- Xidan Li
- Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Department of Medicine, Karolinska Institutet
- Lorenz M. Mayr
- Discovery Sciences, R&D, AstraZeneca
- Kate Wickson
- Discovery Sciences, R&D, AstraZeneca
- Karin Jennbacken
- Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca
- Kenny Hansson
- Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca
- Regina Fritsche-Danielson
- Bioscience Cardiovascular, Research and Early Development, Cardiovascular, Renal and Metabolism (CVRM), BioPharmaceuticals R&D, AstraZeneca
- James Hunt
- Discovery Sciences, R&D, AstraZeneca
- Kenneth R. Chien
- Karolinska Institutet/AstraZeneca Integrated Cardio Metabolic Centre (KI/AZ ICMC), Department of Medicine, Karolinska Institutet
- DOI
- https://doi.org/10.1038/s41467-022-29703-9
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 18
Abstract
Here the authors use modified RNA and VHH libraries to generate intrabodies that target dysregulated interactions between two calcium handling proteins in failing cardiomyocytes. Heart specific expression of the intrabodies in a murine heart failure model results in improved cardiac function.
