Stability of Therapeutic Enzymes: Challenges and Recent Advances

  • Shubhrima Ghosh
  • Shahenvaz Alam
  • Anurag S. Rathore
  • S. K. KhareEmail author
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1148)


Enzymes are biocatalysts that have found profound applications in the current biotherapeutic industry and play a crucial role in diagnosis, prevention, and biochemical analysis of major diseases. However, stability, protein degradation and immunogenicity in the body present unique challenges that are faced upon sustained use of such enzymes. The present chapter is an attempt to dissect the state-of-the-art in relation to the challenges of development of therapeutic enzymes and the recent advances to address them. At the very outset, diseases where enzymes have found effective applications and the various causes of enzyme instability have been discussed. In recent times, polymer or nano- conjugated resistant delivery methods, as well as mutagenesis have led to manifold increase in enzyme stability against thermal denaturation, acidic gut environment, proteolysis and immunogenicity. Further, methods of analytical characterization of proteins have been highlighted and explored to shape future research directions.


Enzyme Metabolic disorders Immunogenicity Protein denaturation Mutagenesis 



United States


Food and drug administration


Acute Myeloid Leukemia


Acute Lymphoblastic Leukemia


Polyethylene glycol


Adenosine Diphosphate


Nicotinamide Adenine Dinucleotide


Enzyme Replacement Therapy




Deoxyribonucleic Acid


Lysosomal Acid Lipase




Lysosomal Acid Lipase


Severe Combined Immune Deficiency


Adenosine Deaminase


Pleuroparenchymal Fibroelastosis


Ribonucleic Acid


Deubiquitinating Enzyme




Binding Antibodies


Gaucher’s Disease


Galactokinase 1


Enzyme Commission


Adenosine Triphosphate


Albumin-Binding Domain






Magnetic Nanoparticles


Poly-Acrylamide Gel Electrophoresis


Sodium Dodecyl Sulfate


Isoelectric Focusing




Difference Gel Electrophoresis


High-performance liquid chromatography


Circular Dichroism


Nuclear Magnetic Resonance


X-ray Diffraction


Fourier-Transform Infrared Spectroscopy




Dynamic Light Scattering


High- Throughput Dynamic Light Scattering


Ultraviolet Resonance Raman


Raman Optical Activity


8-Anilinonaphthalene-1-sulfonic acid




Transmission Electron Microscopy


Enzyme-Linked Immunosorbent Assay


Surface Plasmon Resonance


Bio-Layer Interferometry


Isothermal Titration Calorimetry


Tissue Plasminogen Activator




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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • Shubhrima Ghosh
    • 1
  • Shahenvaz Alam
    • 1
  • Anurag S. Rathore
    • 2
  • S. K. Khare
    • 1
    Email author
  1. 1.Enzyme and Microbial Biochemistry Laboratory, Department of ChemistryIndian Institute of Technology DelhiNew DelhiIndia
  2. 2.Department of Chemical EngineeringIndian Institute of Technology DelhiNew DelhiIndia

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