Title : Antibody-Proteases as a generation of unique biomarkers, biocatalysts, potential targets and translational tools towards nanodesign-driven biochemical engineering and precision medical practice
Abstract:
The identification, impact and implementation of diagnostic, predictive and prognostic biomarkers of the next step generation becomes the Holy Grail of platforms, algorithms and protocols, which are the crucial for Personalized & Precision Medicine (PPM). High impact of Ab-proteases can be used to monitor both clinical and subclinical courses of chronic autoimmune inflammation to predict stepwise transformations of the course, starting from the pre-illness and to prognosticate the clinical illness finally. This information can allow to design the algorithms for combinatorial (preventive, prophylactic, therapeutic and rehabilitative) treatment, whilst developing unique tools for individually therapy for a number of diseases, such as a group of autoimmune diseases which holds a particular position.
Abs endowed with enzymatic properties have been isolated from the serum of patients with different autoimmune conditions. Disease-associated abzymes may have been "induced" by the Ag implicated in the disease and might precisely control a wide variety of physiological processes and thus are important drug targets. Regarding abzymes, their phenomenal property mentioned is buried in the Fab-fragment of the Ig molecule and is appearing to sound as a functional (Ag-binding and enzymatic) property of the Ab molecule.
The primary translational potential of abzymes (Ab-proteases, predominantly) and thus of this knowledge is in the rational design of new therapeutics to exploit the role of the key pathways in influencing disease. The latter is a brand-new field of chemical engineering. For instance, abzymes can selectively cleave the peptide bonds of the virus coat protein, thereby preventing the virus from binding to target cells.
Of tremendous value are Ab-proteases directly affecting remodeling of tissues. By changing sequence specificity one may reach reduction of a density of the negative proteolytic effects within the myelin sheath and thus minimizing scales of demyelination.
Selective chemical modification of abzymes can be used to create novel proteins, particularly enzymes and Abs, with altered specificities and catalytic activities. Abzymes can be chemically engineered to make proteins of higher affinity or smaller molecular variants that retain or change the functional properties of the original Ab. In this context, targeted Ab-mediated proteolysis could thus be applied to isolate from Ig molecules catalytic domains containing segments to exert proteolytic activity and then be used as therapeutic modifiers. Ab-based therapeutics have entered the central stage of drug discovery as a result of a major shift in focus of many biotech and biopharma companies. Modification strategies should soon yield a wide spectrum of novel biomolecules whose activities are optimized for therapeutic applications.
Ab-proteases can be programmed and reprogrammed to suit the needs of the body metabolism or be designed for the development of principally new catalysts with no natural counterparts. Thus, abzyme study has an important value in theory and practice for biology, chemistry and medicine. So, further studies on targeted Ab-mediated proteolysis may provide biomarkers of new generations and thus a supplementary tool for assessing the disease progression and predicting disability of the patients and persons-at-risks. And the new approach is needed to secure artificial or edited Ab-proteases as unique translational probes to diagnose, to monitor, to control and to treat and rehabilitate autoimmune conditions patients at clinical stages and to prevent the disorder at subclinical stages in persons-at-risks to secure the efficacy of preventive, prophylactic and restorative manipulations.
