The identification of the release of paracrine-acting proteins as one mechanism by which cell-based therapies in the heart may improve cardiac function 3 has spurred renewed interest in protein-based therapeutic approaches for cardiac repair.Īlthough protein therapeutics are increasingly becoming mainstream in a number of fields, including cancer and inflammatory diseases, (9 of the 20 top-selling drugs in 2012 were proteins 4) proteins have relatively low penetration in the cardiovascular market. Nonetheless, the reported efficacy of cardiac cell–based therapies in human trials has generated interest in additional therapeutic development pathways. 1, 2 However, the mechanism of action of cell-based therapies remains unclear, and many details with regard to characterization, quality control, and delivery of cells remain to be worked out before widespread therapeutic application. Most notably, clinical trials of cell-based cardiovascular therapy have garnered much attention, and preliminary results are encouraging. Further, we address the promise of applying emerging protein engineering technologies to cardiovascular medicine and the barriers that must be overcome to enable the ultimate success of this approach.Īn explosion of interest in new therapies for heart repair has occurred recently. In this review, we discuss the role of engineered proteins in cardiovascular therapies to date. However, protein engineering as a strategy has not yet been used in the development of cardiovascular therapeutics to the degree that it has been used in other fields. Protein engineering has been used broadly to overcome weaknesses traditionally associated with protein therapeutics and has the potential to specifically enhance the efficacy of molecules for cardiac repair. However, proteins are often limited in their therapeutic potential by short local half-lives and insufficient bioavailability and bioactivity, and many academic laboratories studying cardiovascular diseases are more comfortable with molecular and cellular biology than with protein biochemistry. In addition to the progression of stem cell–based approaches and gene therapy/silencing methods, evidence continues to emerge that protein therapeutics may be used to directly promote cardiac repair and even regeneration. Customer Service and Ordering InformationĪ number of new and innovative approaches for repairing damaged myocardium are currently undergoing investigation, with several encouraging results.Stroke: Vascular and Interventional Neurology.Journal of the American Heart Association (JAHA).Circ: Cardiovascular Quality & Outcomes.Arteriosclerosis, Thrombosis, and Vascular Biology (ATVB).The principle aim of this Review is to present the foundational research that has driven artificial glycoprotein-based targeting and subsequent adaptations with potential therapeutic applications. This has either been done through adopting the glycoprotein scaffold as a drug carrier, or to directly glycosylate therapeutic proteins/enzymes to localize their biological activity. To exploit the knowledge gained from these studies, numerous groups thus became engaged in developing targeted drug methodologies based on the use of artificial glycoproteins. Additionally, binding trends with regard to cancer cell selectivity were also investigated. As a result, the organ-specific accumulation for a variety of glycoproteins decorated with simple and/or complex glycans was identified. To gain a better understanding of the factors that govern in vivo recognition, artificial glycoproteins were initially created to probe changes made to the accumulation and biodistribution of specific glycan assemblies through biomimicry. Akin to a cellular “fingerprint,” the glycocalyx is a glycan-enriched cellular coating that plays a crucial role in mediating cell-to-cell interactions.
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