Comparison of adeno-associated virus serotypes and delivery methods for cardiac gene transfer
Open accessAbstract
Cardiac gene transfer is a potentially useful strategy for cardiovascular diseases. The adeno-associated virus (AAV) is a common vector to obtain transgene expression in the heart. Initial studies conducted in rodents used indirect intracoronary delivery for cardiac gene transfer. More recently AAV vectors with so-called cardiac tropism have enabled significant cardiac transgene expression following intravenous injection. However, a direct comparison of intravenous versus intracoronary delivery with rigorous quantification of cardiac transgene expression has not been conducted. In the present study we tested the hypothesis that intracoronary AAV delivery would be superior to intravenous delivery vis-à-vis cardiac transgene expression. We compared intravenous and intracoronary delivery of AAV5, AAV6, and AAV9 (5×1011 genome copies per mouse). Using enhanced green fluorescent protein as a reporter, we quantified transgene expression by fluorescence intensity and Western blotting. Quantitative polymerase chain reaction (PCR) was also performed to assess vector DNA copies, employing primers against common sequences on AAV5, AAV6, and AAV9. Intracoronary delivery resulted in 2.6- to 28-fold higher transgene protein expression in the heart 3 weeks after AAV injection compared to intravenous delivery depending on AAV serotype. The highest level of cardiac gene expression was achieved following intracoronary delivery of AAV9. Intracoronary delivery of AAV9 is a preferred method for cardiac gene transfer. Fang and colleagues conduct a direct comparison between intravenous and intracoronary delivery of adeno-associated virus (AAV) vector for cardiac gene transfer. Mice were injected with AAV serotypes 5, 6, and 9 carrying a reporter gene, and gene expression was quantified. Intracoronary delivery resulted in 2.6- to 28-fold higher protein expression in the heart, with AAV9 displaying the highest levels.
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AAV-9 has superior cardiotropism than other serotypes in small rodents.
“AAV-9 has been shown to have superior cardiotropism than other serotypes in small rodents”
From Small and large animal models in cardiac contraction research: advantages and disadvantages (2014) · cites this paper as Fang, et al., 2012
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AAV Vector Toolkit for the Delivery and Expression of the Artificial microRNA in the Murine Heart
Galkin, I. I., Skopenkova, V. V., Shubina, M. Y., Polikarpova, A. V., Vassilieva, S. G., Savchenko, I. M., Лебедева, О. С., Goliusova, D. V., Sharikova, M. Y., Gureev, V. V., et al. (2026) · BioTech · doi:10.3390/biotech15030055
- Authors
- Fang, H., Lai, N. C., Gao, M. H., Miyanohara, A., Roth, D. M., Tang, T., & Hammond, H. K.
- Affiliations
- University of California San Diego (US)
- Corresponding author
- Hammond, H. Kirk
- Venue
- Human Gene Therapy Methods
- Publisher
- SAGE Publications
- Published
- 2012-08
- Volume
- 23
- Issue
- 4
- Pages
- 234-241
- ISSN
- 1946-6536 (ISSN-L)
- 1946-6544
- PMC
- PMC3555516
- OpenAlex
- W2018977972
- Cited by
- 58
- References
- 36
- Citations by year
- 2026: 4 · 2025: 6 · 2024: 6 · 2023: 3 · 2022: 3 · 2021: 3 · 2020: 3 · 2019: 5 · 2018: 2 · 2017: 2 · 2016: 6 · 2015: 7 · 2014: 1 · 2013: 6 · 2012: 1
- FWCI
- 2.88
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Human Gene Therapy Methods (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- U.S. Department of Veterans Affairs
- American Heart Association
- National Institutes of Health
- Veterans Affairs San Diego Healthcare System
- National Heart, Lung, and Blood Institute (R01HL081741, HL 081741, HL088426, R01HL088426, P01HL066941)
- 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
- adeno-associated virus vectors, cardiac gene transfer, AAV serotypes, AAV5, AAV6, AAV9, intravenous delivery, transgene expression, EGFP reporter, cardiovascular disease
- MeSH terms
- Dependovirus, Animals, Genetic Vectors, Injections, Intravenous, Liver, Male, Mice, Inbred C57BL, Myocardium, Serotyping, Gene Transfer Techniques, Green Fluorescent Proteins, Mice
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