Gene Therapy Approaches to Biological Pacemakers
Abstract
:1. Introduction
2. Prerequisites for the Generation of a Biological Pacemaker
3. Cell-Based Approaches to Biological Pacemakers
4. General Principles of Myocardial Gene Therapy
4.1. Vectors
Improving rAAV Delivery Vectors
4.2. Vector Delivery to Myocardium
4.2.1. Epicardial Painting
4.2.2. Epicardial Injection
4.2.3. Selective Intracoronary Perfusion
4.2.4. Intramyocardial Injection
5. Gene Therapy Approaches to Biological Pacemakers
5.1. Receptor-Based Gene Therapy Apporach
5.2. Channel-Based Gene Therapy Approaches
5.2.1. Kir2.1 Channel Downregulation (Kir2.1AAA)
5.2.2. HCN Overexpression
5.3. Combined Gene-Cell Approaches
5.4. Somatic Reprogramming to an Induced Pacemaker-Like Phenotype
6. RNA and Small Molecule-Based Therapy Approaches
7. Limitations of Gene Therapy Use for Biological Pacemakers
8. Conclusions
Funding
Conflicts of Interest
References
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Vector | Plasmid | AAV | Lentivirus | Adenovirus |
---|---|---|---|---|
Maximum titre (particles per mL) | N/A | Up to 1013 | Up to 109 | Up to 1013 |
Genome/Size (Kb) | DNA | ssDNA | ssRNA | dsDNA |
Insert capacity | 15 kB | 4.8 kB | 10 kB | 7 to 30 kB |
Integration | No | No | Yes (Random) | No |
Length of transgene expression | Up to 2 Months | Long Term | Long Term | Up to 2 Weeks |
Immunogenicity | Minimally Immunogenic | Minimally Immunogenic | Minimally Immunogenic | Cytotoxic and Immunogenic |
Limited by neutralizing antibodies | No | Yes | No | No |
Target cells | Dividing and Non-dividing cells | Dividing and Non-dividing cells | Dividing and Non-dividing cells | Dividing and Non-dividing cells |
Cardiac gene transfer | Low Cardiac Transduction | Cardiotropic AAV Serotypes | Lower Cardiac Transduction | High Cardiac Transduction |
Disadvantages | Low Transfection Efficiency | Risk of neutralizing antibodies and T-Cell Responses | Risk of insertional mutagenesis | High antibody and inflammatory response |
Clinical trial approval | Yes | Yes | Yes | Yes |
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Farraha, M.; Kumar, S.; Chong, J.; Cho, H.C.; Kizana, E. Gene Therapy Approaches to Biological Pacemakers. J. Cardiovasc. Dev. Dis. 2018, 5, 50. https://doi.org/10.3390/jcdd5040050
Farraha M, Kumar S, Chong J, Cho HC, Kizana E. Gene Therapy Approaches to Biological Pacemakers. Journal of Cardiovascular Development and Disease. 2018; 5(4):50. https://doi.org/10.3390/jcdd5040050
Chicago/Turabian StyleFarraha, Melad, Saurabh Kumar, James Chong, Hee Cheol Cho, and Eddy Kizana. 2018. "Gene Therapy Approaches to Biological Pacemakers" Journal of Cardiovascular Development and Disease 5, no. 4: 50. https://doi.org/10.3390/jcdd5040050
APA StyleFarraha, M., Kumar, S., Chong, J., Cho, H. C., & Kizana, E. (2018). Gene Therapy Approaches to Biological Pacemakers. Journal of Cardiovascular Development and Disease, 5(4), 50. https://doi.org/10.3390/jcdd5040050