Single chain fragment variable, a new theranostic approach for cardiovascular diseases

Abstract

Cardiovascular diseases (CVDs) remain a significant global health challenge, leading to substantial morbidity and mortality. Despite recent advancements in CVD management, pharmaceutical treatments often suffer from poor pharmacokinetics and high toxicity. With the rapid progress of modern molecular biology and immunology, however, single-chain fragment variable (scFv) molecule engineering has emerged as a promising theranostic tool to offer specificity and versatility in targeting CVD-related antigens. To represent the latest development on the potential of scFv in the context of CVDs, this review summarized the new mechanism of action and applications as therapeutic, as well as diagnostic agents. Furthermore, the advantages of scFv, including its small size, ease of modification, and ability to be engineered for enhanced affinity and specificity, are also described. Finally, such challenges as immunogenicity, stability, and scalability, alongside strategies to overcome these hurdles, are deeply scrutinized to provide safer and more effective strategies for the diagnosis and treatment of the incurable CVDs.

Keywords: antibody engineering; cardiovascular diseases; diagnostics; single-chain fragment variable; therapeutics.

Figure 1

Schematic representation of full-length antibody and structural diversity of antibody Fab fragments and scFv formats. (A) Full-length antibody structure showcases the heavy and light chains, the variable (V), and constant regions with structural diversity of antibody Fab fragments. (B) scFv and its various engineered formats, including diabody, triabody, tetrabody, minibody, and scFv-Fc.

Figure 2

scFv-based strategies to target atherosclerotic plaque. scFv molecules could potentially bind to endothelial cells, macrophages, dendritic cells, foam cells, necrotic cells, and platelets, illustrating the ameliorative potential of scFv to neutralize targets and mitigate the progression of atherosclerosis.

Figure 3

scFv as a theranostic agent in CVDs. This figure provides a multifaceted view of CVDs depicting (A) common risk factors contributing to CVDs, including obesity, diabetes, smoking, and drug-induced hypertension, (B) the different production techniques of scFv antibodies, (C) different types of scFv antibodies for therapeutics, (D) the cutting-edge integration of scFv with nanoparticles and microbubbles, a leap forward in diagnostic methodologies, and (E) a healthy individual with a healthy heart, a testament to the successful application of scFv-based theranostics.

Figure 4

Properties required for ideal theranostic scFv. This figure illustrates the ideal properties of scFvs for theranostic applications, including their versatility in size like bispecific, tri-specific, and tetra-specific configurations, which enable targeting multiple antigens simultaneously. The scFvs specificity ensures precise targeting of disease markers, while low immunogenicity is reflected in the limited recognition by macrophages, reducing the immune response. Scalability is highlighted by their high production capacity, supporting large-scale manufacturing. Additionally, the integration of scFvs with nanoparticles underscores their role in enhancing diagnostic capabilities.