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Production and Purification of Therapeutic Enzymes

  • M. Ângela TaipaEmail author
  • Pedro Fernandes
  • Carla C. C. R. de Carvalho
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1148)

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.

Keywords

Therapeutic enzyme Human therapy Recombinant Engineering Production Purification 

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

Notes

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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Copyright information

© Springer Nature Singapore Pte Ltd. 2019

Authors and Affiliations

  • M. Ângela Taipa
    • 1
    Email author
  • Pedro Fernandes
    • 1
    • 2
  • Carla C. C. R. de Carvalho
    • 1
  1. 1.iBB-Institute for Biosciences and Bioengineering, Department of Bioengineering, Instituto Superior TécnicoUniversidade de LisboaLisbonPortugal
  2. 2.Faculty of EngineeringUniversidade Lusófona de Humanidades e TecnologiasLisbonPortugal

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