Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine

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dc.contributor.authorMarsh, Spencer R.en
dc.contributor.authorWilliams, Zachary J.en
dc.contributor.authorPridham, Kevin J.en
dc.contributor.authorGourdie, Robert G.en
dc.contributor.departmentFralin Biomedical Research Instituteen
dc.contributor.departmentBiomedical Engineering and Mechanicsen
dc.contributor.departmentSchool of Medicineen
dc.date.accessioned2021-05-14T13:14:58Zen
dc.date.available2021-05-14T13:14:58Zen
dc.date.issued2021-05-05en
dc.date.updated2021-05-13T14:34:54Zen
dc.description.abstractConnexin (Cx43)-formed channels have been linked to cardiac arrhythmias and diseases of the heart associated with myocardial tissue loss and fibrosis. These pathologies include ischemic heart disease, ischemia-reperfusion injury, heart failure, hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and Duchenne muscular dystrophy. A number of Cx43 mimetic peptides have been reported as therapeutic candidates for targeting disease processes linked to Cx43, including some that have advanced to clinical testing in humans. These peptides include Cx43 sequences based on the extracellular loop domains (e.g., Gap26, Gap 27, and Peptide5), cytoplasmic-loop domain (Gap19 and L2), and cytoplasmic carboxyl-terminal domain (e.g., JM2, Cx43tat, CycliCX, and the alphaCT family of peptides) of this transmembrane protein. Additionally, RYYN peptides binding to the Cx43 carboxyl-terminus have been described. In this review, we survey preclinical and clinical data available on short mimetic peptides based on, or directly targeting, Cx43, with focus on their potential for treating heart disease. We also discuss problems that have caused reluctance within the pharmaceutical industry to translate peptidic therapeutics to the clinic, even when supporting preclinical data is strong. These issues include those associated with the administration, stability in vivo, and tissue penetration of peptide-based therapeutics. Finally, we discuss novel drug delivery technologies including nanoparticles, exosomes, and other nanovesicular carriers that could transform the clinical and commercial viability of Cx43-targeting peptides in treatment of heart disease, stroke, cancer, and other indications requiring oral or parenteral administration. Some of these newly emerging approaches to drug delivery may provide a path to overcoming pitfalls associated with the drugging of peptide therapeutics.en
dc.description.notesCorrected version issued 2022-04-16.en
dc.description.versionPublished versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationMarsh, S.R.; Williams, Z.J.; Pridham, K.J.; Gourdie, R.G. Peptidic Connexin43 Therapeutics in Cardiac Reparative Medicine. J. Cardiovasc. Dev. Dis. 2021, 8, 52.en
dc.identifier.doihttps://doi.org/10.3390/jcdd8050052en
dc.identifier.urihttp://hdl.handle.net/10919/103291en
dc.language.isoenen
dc.publisherMDPIen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectconnexin43en
dc.subjectpeptideen
dc.subjectcardiac diseaseen
dc.subjectcardiac therapeuticen
dc.subjectdrug deliveryen
dc.titlePeptidic Connexin43 Therapeutics in Cardiac Reparative Medicineen
dc.title.serialJournal of Cardiovascular Development and Diseaseen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten
dc.type.dcmitypeStillImageen

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