Introducing Genes to the Heart: All About Delivery
Open accessAbstract
Recent clinical gene therapy trials for the treatment of heart failure have failed to meet primary efficacy endpoints and have tampered enthusiasm for the future application of cardiac gene therapy. These results have brought to light the difficulty of efficiently introducing genes into the human heart and have focused on potential problems that need to be addressed before further clinical applications. These trials however have established the safety of gene delivery vectors for cardiac targeting in humans. The sinusoidal trajectory of gene therapy continues and despite these setbacks the future of the field is promising.
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The human mini-heart models provide a relevant platform for dosage optimization, considering that results from animal experiments regarding effectiveness of cardiac gene transfer do not predict human myocardial transduction efficiency.
“Our human mini-heart models also provide a relevant platform for dosage optimization, considering that results from animal experiments regarding effectiveness of cardiac gene transfer do not predict human myocardial transduction efficiency.77”
From Reversal of contractile defects by mediating calcium homeostasis in human mini-heart models of heart failure with preserved ejection fraction (HFpEF) leads to first-in-human gene therapy clinical trial (2024) · cites this paper as [77]
The “Gene delivery: Critical step” section reports that human hearts in the CUPID IIb trial had much lower vector uptake than animal models that had shown therapeutic efficacy. This supports caution in extrapolating animal results, but the paper documents that discrepancy for a particular trial rather than establishing that animal experiments generally cannot predict human myocardial transduction efficiency. The human mini-heart platform is the citing authors’ own proposal, not a finding attributed to this source. (LLM, conf=0.84)
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Cites
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Costa, K. D., Wong, A. O. T., Mak, S. Y., Roberts, E. G., Keung, W., Correia, C., Walentinsson, A., Christoffersson, J., Cheung, A., Lieu, D. K., et al. (2024) · bioRxiv · doi:10.1101/2024.08.27.609034 · Cited by 5 · see citing works
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- Authors
- Hajjar, R. J., & Ishikawa, K.
- Affiliations
- Icahn School of Medicine at Mount Sinai (US)
- Venue
- Circulation Research
- Published
- 2017-01-06
- Volume
- 120
- Issue
- 1
- Pages
- 33-35
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC5221570
- OpenAlex
- W2569554011
- Cited by
- 36
- References
- 15
- Citations by year
- 2026: 1 · 2025: 5 · 2024: 5 · 2023: 3 · 2022: 2 · 2021: 2 · 2020: 4 · 2019: 2 · 2018: 5 · 2017: 7
- FWCI
- 3.26
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Fondation Leducq
- National Institutes of Health (128072)
- National Heart, Lung, and Blood Institute (P20HL100396, R01HL119046, R01HL129814, P50HL112324, HL-119046, HL129814, R01HL128072, T32HL007824, HL117505, R01HL117505, HL112324, R01HL128099, R01HL131404)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Virus-based gene therapy research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Interference and Gene Delivery
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- cardiac gene therapy, heart failure, gene delivery vectors, gene delivery efficiency, vector safety
- MeSH terms
- Animals, Clinical Trials as Topic, Heart Failure, Humans, Genetic Therapy, Gene Transfer Techniques
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