Intrabodies (both single-chain Fv and single-domain VH, VHH, and VL nanobodies) offer solutions to pharmacodynamics and target engagement posed by immunotherapeutics. Constructs use fusions with peptides that can re-target antigen-antibody complexes to enhance therapeutic activity. Fusions with proteolytic targeting signals, such as the activation and inactivation of regulatory proteins involved in signaling pathways to cell growth, differentiation, stress responses and cell death programs (PEST degron), such fusions enhancing potency in some cases. Stem cell transplants can be protected from exogenous misfolded proteins by stable transfection with intrabodies. Erythrocytes function in the clearing of the blood of complement-bearing immune complexes and pathogens and thus have antiinflammatory potential. This potential is impaired in elderly probands as the Gershons (Israel Institute of Technology) have discovered some 30 years ago
In fact, exposure to complement-bearing immune complexes enhances the in vitro sequestration of erythrocytes from young but not elderly donors. With protein glycation at stake we begin, in the year 2021, to understand functional alterations of any protein and hope is risen to influence a given proteins’ function.
This defect in the ability to clear immune complexes and micro-organisms bearing C3b from the circulation should render the seniors again in a position to cope with varied pathologies including infection, inflammation and concomitant damage to the vascular tissue – commonly observed in the elderly. This is called by some as reprogramming the aging phenotype