“…This represents an advantage for in vivo imaging because rapidly reduces the background signal but it is the major shortcoming for therapeutic applications. However, the recombinant nature of nanobodies can be exploited to produce fusions with relevant proteins and tags that possess reduced clearance and even additional useful functions such as fluorescence or cytotoxicity or enable the building of multivalent and multi-specific constructs with largely diversified formats ( 10 , 196 – 198 ). Multi-specific nanobodies retain at least part of the advantages of nanobodies, providing a mass that is still significantly smaller than IgGs and the capacity of targeting hidden epitopes by means of their protruding paratopes.…”
Recombinant antibodies such as nanobodies are progressively demonstrating to be a valid alternative to conventional monoclonal antibodies also for clinical applications. Furthermore, they do not solely represent a substitute for monoclonal antibodies but their unique features allow expanding the applications of biotherapeutics and changes the pattern of disease treatment. Nanobodies possess the double advantage of being small and simple to engineer. This combination has promoted extremely diversified approaches to design nanobody-based constructs suitable for particular applications. Both the format geometry possibilities and the functionalization strategies have been widely explored to provide macromolecules with better efficacy with respect to single nanobodies or their combination. Nanobody multimers and nanobody-derived reagents were developed to image and contrast several cancer diseases and have shown their effectiveness in animal models. Their capacity to block more independent signaling pathways simultaneously is considered a critical advantage to avoid tumor resistance, whereas the mass of these multimeric compounds still remains significantly smaller than that of an IgG, enabling deeper penetration in solid tumors. When applied to CAR-T cell therapy, nanobodies can effectively improve the specificity by targeting multiple epitopes and consequently reduce the side effects. This represents a great potential in treating malignant lymphomas, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma and solid tumors. Apart from cancer treatment, multispecific drugs and imaging reagents built with nanobody blocks have demonstrated their value also for detecting and tackling neurodegenerative, autoimmune, metabolic, and infectious diseases and as antidotes for toxins. In particular, multi-paratopic nanobody-based constructs have been developed recently as drugs for passive immunization against SARS-CoV-2 with the goal of impairing variant survival due to resistance to antibodies targeting single epitopes. Given the enormous research activity in the field, it can be expected that more and more multimeric nanobody molecules will undergo late clinical trials in the next future.Systematic Review Registration
“…This represents an advantage for in vivo imaging because rapidly reduces the background signal but it is the major shortcoming for therapeutic applications. However, the recombinant nature of nanobodies can be exploited to produce fusions with relevant proteins and tags that possess reduced clearance and even additional useful functions such as fluorescence or cytotoxicity or enable the building of multivalent and multi-specific constructs with largely diversified formats ( 10 , 196 – 198 ). Multi-specific nanobodies retain at least part of the advantages of nanobodies, providing a mass that is still significantly smaller than IgGs and the capacity of targeting hidden epitopes by means of their protruding paratopes.…”
Recombinant antibodies such as nanobodies are progressively demonstrating to be a valid alternative to conventional monoclonal antibodies also for clinical applications. Furthermore, they do not solely represent a substitute for monoclonal antibodies but their unique features allow expanding the applications of biotherapeutics and changes the pattern of disease treatment. Nanobodies possess the double advantage of being small and simple to engineer. This combination has promoted extremely diversified approaches to design nanobody-based constructs suitable for particular applications. Both the format geometry possibilities and the functionalization strategies have been widely explored to provide macromolecules with better efficacy with respect to single nanobodies or their combination. Nanobody multimers and nanobody-derived reagents were developed to image and contrast several cancer diseases and have shown their effectiveness in animal models. Their capacity to block more independent signaling pathways simultaneously is considered a critical advantage to avoid tumor resistance, whereas the mass of these multimeric compounds still remains significantly smaller than that of an IgG, enabling deeper penetration in solid tumors. When applied to CAR-T cell therapy, nanobodies can effectively improve the specificity by targeting multiple epitopes and consequently reduce the side effects. This represents a great potential in treating malignant lymphomas, acute myeloid leukemia, acute lymphoblastic leukemia, multiple myeloma and solid tumors. Apart from cancer treatment, multispecific drugs and imaging reagents built with nanobody blocks have demonstrated their value also for detecting and tackling neurodegenerative, autoimmune, metabolic, and infectious diseases and as antidotes for toxins. In particular, multi-paratopic nanobody-based constructs have been developed recently as drugs for passive immunization against SARS-CoV-2 with the goal of impairing variant survival due to resistance to antibodies targeting single epitopes. Given the enormous research activity in the field, it can be expected that more and more multimeric nanobody molecules will undergo late clinical trials in the next future.Systematic Review Registration
“…The expression of nanobodies and, more and more frequently, nanobodies fused to tags offering orthogonal functions, becomes constantly more diversified [32,130]. This is necessary to obtain reagents that possess the highly differentiated features necessary for fulfilling the always new final application requirements and consequently their production relies on alternative expression conditions [47].…”
Section: Discussionmentioning
confidence: 99%
“…Fusion immunoreagents are either ready-to-use or suitable for controlled custom functionalization with modular chemical partners ( Fig. 1) [30][31][32]. For instance, a tag such as SNAP allows the 1:1 nanobody derivatization with any molecule presenting an O 6 -benzylguanine group.…”
A B S T R A C TAntibody fragments for which the sequence is available are suitable for straightforward engineering and expression in both eukaryotic and prokaryotic systems. When produced as fusions with convenient tags, they become reagents which pair their selective binding capacity to an orthogonal function. Several kinds of immunoreagents composed by nanobodies and either large proteins or short sequences have been designed for providing inexpensive ready-to-use biological tools. The possibility to choose among alternative expression strategies is critical because the fusion moieties might require specific conditions for correct folding or posttranslational modifications. In the case of nanobody production, the trend is towards simpler but reliable (bacterial) methods that can substitute for more cumbersome processes requiring the use of eukaryotic systems. The use of these will not disappear, but will be restricted to those cases in which the final immunoconstructs must have features that cannot be obtained in prokaryotic cells. At the same time, bacterial expression has evolved from the conventional procedure which considered exclusively the nanobody and nanobody-fusion accumulation in the periplasm. Several reports show the advantage of cytoplasmic expression, surface-display and secretion for at least some applications. Finally, there is an increasing interest to use as a model the short nanobody sequence for the development of in silico methodologies aimed at optimizing the yields, stability and affinity of recombinant antibodies.
“…The common materials for the removal of different types of pollutants include activated carbons [6][7][8], zeolites [9], ion exchange resins [10], and modified biomass or derived adsorbents [11] or biomass-derived nanocomposites [12,13]. In recent years, there has been increased focus on variety of nanomaterials, nanocomposites, and nanomaterials modifications including biomodification and intensification [2,[14][15][16][17][18][19][20][21].…”
Section: Why Nanomaterials and Nanocomposites?mentioning
Nanotechnology is expected to play a major role practically in all aspects of life and will be overlapping many areas of science and engineering. Presently, the applications of nanomaterials especially in water and wastewater treatment are rather limited. Water is a major resource and its quality is crucial to life since
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