Gene Therapy Approaches to Biological Pacemakers

Farraha, Melad; Kumar, Saurabh; Chong, James J.H.; Cho, Hee Cheol; Kizana, Eddy

doi:10.3390/jcdd5040050

Cited by 9 publications

(15 citation statements)

References 115 publications

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“…Gene and cell therapies spark the development of biological pacemakers, which may address such limitations [2]. It is well known that the sinoatrial node (SAN) is the origin of cardiac electrical activity and sets the rhythm for the heart.…”

Section: Introductionmentioning

confidence: 99%

Genetically Modified Porcine Mesenchymal Stem Cells by Lentiviral Tbx18 Create a Biological Pacemaker

Liu

et al. 2019

Stem Cells International

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Background Tbx18 is a vital transcription factor involved in embryonic sinoatrial node (SAN) formation process but is gradually vanished after birth. Myocardial injection of lentiviral Tbx18 converts cardiomyocytes into pacemaker-like cells morphologically and functionally. In this in vitro and in vivo study, genetical modification of porcine bone mesenchymal stem cells (BMSCs) by recapturing the Tbx18 expression creates a biological pacemaker which was examined. Methods The isolated porcine BMSCs were transfected with lentiviral Tbx18, and the induced pacemaker-like cells were analyzed using real-time polymerase chain reaction and western blotting to investigate the efficiency of transformation. Then, the induced pacemaker-like cells were implanted into the right ventricle of the SAN dysfunction porcine model after the differentiation process. Biological pacemaker activity and ectopic pacing region were tested by an electrocardiograph (ECG) monitor. Results The isolated porcine BMSCs expressed specific surface markers of stem cells; meanwhile, the expression of myocardial markers was upregulated significantly after lentiviral Tbx18 transfection. The porcine SAN dysfunction model was constructed by electrocoagulation using a surgical electrotome. The results showed that the mean heart beat (HR) of BMSCs-Tbx18 was significantly higher than that of BMSCs-GFP. An ectopic pacing region was affirmed into the right ventricle by ECG after implantation of BMSCs-Tbx18. Conclusion It was verified that Lenti-Tbx18 is capable of transducing porcine BMSCs into pacemaker-like cells. Genetically modified porcine BMSCs by lentiviral Tbx18 could create a biological pacemaker. However, further researches in large-scale animals are required to rule out unexpected complications prior to application in clinical practice.

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Section: Introductionmentioning

confidence: 99%

Genetically Modified Porcine Mesenchymal Stem Cells by Lentiviral Tbx18 Create a Biological Pacemaker

Liu

et al. 2019

Stem Cells International

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“…DNA-signatures enhanced by ZK-based proofs may be extended to different GM organisms or agents. Of special interest here may be emerging pharmaceutical or medical applications, including medicinal products, gene therapy for biological pacemakers (Farraha et al, 2018) and for the nervous system (Bowers et al, 2011). The full potential of supporting cyberbiosecurity risks via cryptographic and cybersecurity means still remains to be fully fleshed out (see also Diggans and Leproust, 2019; Richardson et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

On DNA Signatures, Their Dual-Use Potential for GMO Counterfeiting, and a Cyber-Based Security Solution

Mueller¹

2019

Front. Bioeng. Biotechnol.

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This study investigates the role and functionality of special nucleotide sequences (“DNA signatures”) to detect the presence of an organism and to distinguish it from all others. After highlighting vulnerabilities of the prevalent DNA signature paradigm for the identification of agricultural genetically modified (GM) organisms it will be argued that these so-called signatures really are no signatures at all - when compared to the notion of traditional (handwritten) signatures and their generalizations in the modern (digital) world. It is suggested that a recent contamination event of an unauthorized GM Bacillus subtilis strain (Paracchini et al., 2017 ) in Europe could have been—or the same way could be - the consequence of exploiting gaps of prevailing DNA signatures. Moreover, a recent study (Mueller, 2019 ) proposes that such DNA signatures may intentionally be exploited to support the counterfeiting or even weaponization of GM organisms (GMOs). These concerns mandate a re-conceptualization of how DNA signatures need to be realized. After identifying central issues of the new vulnerabilities and overlying them with practical challenges that bio-cyber hackers would be facing, recommendations are made how DNA signatures may be enhanced. To overcome the core problem of signature transferability in bioengineered mediums, it is necessary that the identifier needs to remain secret during the entire verification process. On the other hand, however, the goal of DNA signatures is to enable public verifiability, leading to a paradoxical dilemma. It is shown that this can be addressed with ideas that underlie special cryptographic signatures, in particular those of “zero-knowledge” and “invisibility.” This means more than mere signature hiding, but relies on a knowledge-based proof and differentiation of a secret (here, as assigned to specific clones) which can be realized without explicit demonstration of that secret. A re-conceptualization of these principles can be used in form of a combined (digital and physical) method to establish confidentiality and prevent un-impersonation of the manufacturer. As a result, this helps mitigate the circulation of possibly hazardous GMO counterfeits and also addresses the situation whereby attackers try to blame producers for deliberately implanting illicit adulterations hidden within authorized GMOs.

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“…A suitable delivery method of the selected vector is another essential consideration for gene therapy. Some primary delivery methods being researched include epicardial painting, epicardial injection, and intracoronary perfusion (Farraha et al, 2018).…”

Section: Vector Delivery Methodsmentioning

confidence: 99%

Application of Gene Therapy for Treatment of Atrial Fibrillation

Sequeira

2022

J Stud Res

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Atrial fibrillation is the most common arrhythmia globally and is associated with an increased risk for various other complications. Ablation, one of the most widely used treatments, is irreversible and can damage tissue surrounding the ablation line. Furthermore, many people with structural heart abnormalities or other conditions cannot be effectively treated. The complexity of atrial fibrillation and the uniqueness of each case make a universally effective treatment nearly impossible. The present paper describes the current treatments for atrial fibrillation and assesses the potential of gene therapy as a new clinical treatment. Further research into gene therapy could provide more targeted and effective treatments for atrial fibrillation and many other genetic conditions.

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Gene Therapy Approaches to Biological Pacemakers

Cited by 9 publications

References 115 publications

Genetically Modified Porcine Mesenchymal Stem Cells by Lentiviral Tbx18 Create a Biological Pacemaker

Genetically Modified Porcine Mesenchymal Stem Cells by Lentiviral Tbx18 Create a Biological Pacemaker

On DNA Signatures, Their Dual-Use Potential for GMO Counterfeiting, and a Cyber-Based Security Solution

Application of Gene Therapy for Treatment of Atrial Fibrillation

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