Abstract
The use of therapeutic enzymes embraces currently a vast array of applications, abridging from diggestive disorders to cancer therapy, cardiovascular and lysosomal storage diseases. Enzyme drugs bind and act on their targets with great affinity and specificity, converting substrates to desired products in a reduced time frame with minimal side reactions. These characteristics have resulted in the development of a multitude of enzyme biopharmaceuticals for a wide range of human disorders.
The advances in genetic engineering and DNA recombination techniques facilitated the production of therapeutical human-like enzymes, using different cells as host organisms. The selection of hosts generally privileges those that secrete the enzyme into the culture medium, as this eases the purification process, and those that are able to express complex glycoproteins, with glycosylation patterns and other post-translational modifications close to human proteins. Moreover, engineering approaches such as pegylation, encapsulation in micro- and nanocarriers, and mutation of amino acid residues of the native enzyme molecule to yield variants with improved therapeutic activity, half-life and/or stability, have been also addressed. Engineered enzyme products have been designed to display enhanced delivery to target sites and reduced adverse side-effects (e.g., immunogenicity) upon continuous drug administration.
Irrespectively of the production method, the final formulation of therapeutic enzymes must display high purity and specificity, and they are often marketed as lyophilized pure preparations with biocompatible buffering salts and diluents to prepare the reconstituted aqueous solution before treatment.
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Abbreviations
- Ach:
-
Acetylcholine
- AGS:
-
n-acetylgalactosamine 4-sulfatase
- BSE:
-
Bovine spongiform encephalomyelitis
- CESD:
-
Cholesteryl ester storage disease
- CHO:
-
Chinese hamster ovary
- CocE:
-
Cocaine esterase
- CPD:
-
Computational protein design
- DE:
-
Directed evolution
- DNase:
-
Deoxyribonuclease
- EMEA:
-
European Medicines Agency
- FDA:
-
Food and Drug Administration
- hBche:
-
Human butyrylcholinesterase
- IC50 :
-
Half-maximal inhibitory concentration
- IMAC:
-
Ion metal affinity chromatography
- kcat :
-
Turnover number
- KM :
-
Michaelis–Menten constant
- L-ASNase:
-
L-asparaginase
- MPS:
-
Mucopolysaccharidosis
- PEG:
-
Polyethylene glycol
- PKU:
-
Phenylketonuria
- PMP:
-
Plant-made pharmaceuticals
- SCID:
-
Severe combined immunodeficiency
- SDM:
-
Site-directed mutagenesis
- Tm :
-
Half-inactivation temperature
- tPA:
-
Tissue plasminogen activator
- uPA:
-
Urokinase-type plasminogen activator
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Acknowledgements
CCCR de Carvalho acknowledges Fundação para a Ciência e a Tecnologia, I.P. (FCT), Portugal, for financial support under program “FCT Investigator 2013” (IF/01203/2013/CP1163/CT0002).
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Taipa, M.Â., Fernandes, P., de Carvalho, C.C.C.R. (2019). Production and Purification of Therapeutic Enzymes. In: Labrou, N. (eds) Therapeutic Enzymes: Function and Clinical Implications. Advances in Experimental Medicine and Biology, vol 1148. Springer, Singapore. https://doi.org/10.1007/978-981-13-7709-9_1
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