Articolo in rivista, 2022, ENG, 10.2174/0929867328666210713094722
Cioni Patrizia, Gabellieri Edi, Campanini Barbara, Bettati Stefano and Raboni Samanta
Raboni, S (Corresponding Author), CNR, Inst Biophys, Via Moruzzi 1, I-56124 Pisa, Italy. Raboni, S (Corresponding Author), Univ Parma, SITEIA PARMA Interdept Ctr, Parco Area Sci Bldg 33, I-43124 Parma, Italy. Cioni, Patrizia; Gabellieri, Edi; Bettati, Stefano; Raboni, Samanta, CNR, Inst Biophys, Via Moruzzi 1, I-56124 Pisa, Italy. Campanini, Barbara, Univ Parma, Dept Food & Drug, Parco Area Sci 23-A, I-43124 Parma, Italy. Campanini, Barbara; Bettati, Stefano, Univ Parma, Biopharmanet TEC Interdept Ctr, Parco Area Sci Bldg 33, I-43124 Parma, Italy. Bettati, Stefano, Univ Parma, Dept Med & Surg, Via Volturno 39, I-43125 Parma, Italy. Raboni, Samanta, Univ Parma, SITEIA PARMA Interdept Ctr, Parco Area Sci Bldg 33, I-43124 Parma, Italy.
The development of safe and efficacious enzyme-based human therapies has increased greatly in the last decades, thanks to remarkable advances in the understanding of the molecular mechanisms responsible for different diseases, and the characterization of the catalytic activity of relevant exogenous enzymes that may play a remedial effect in the treatment of such pathologies. Several enzyme-based biotherapeutics have been approved by FDA (the U.S. Food and Drug Administration) and EMA (the European Medicines Agency) and many are undergoing clinical trials. Apart from enzyme replacement therapy in human genetic diseases, which is not discussed in this review, approved enzymes for human therapy find applications in several fields, from cancer therapy to thrombolysis and the treatment, e.g., of clotting disorders, cystic fibrosis, lactose intolerance and collagen-based disorders. The majority of therapeutic enzymes are of microbial origin, the most convenient source due to fast, simple and cost-effective production and manipulation. The use of microbial recombinant enzymes has broadened prospects for human therapy but some hurdles such as high immunogenicity, protein instability, short half-life and low substrate affinity, still need to be tackled. Alternative sources of enzymes, with reduced side effects and improved activity, as well as genetic modification of the enzymes and novel delivery systems are constantly searched. Chemical modification strategies, targeted-and/or nanocarrier-mediated delivery, directed evolution and site-specific mutagenesis, fusion proteins generated by genetic manipulation are the most explored tools to reduce toxicity and improve bioavailability and cellular targeting. This review provides a description of exogenous enzymes that are presently employed for the therapeutic management of human diseases with their current FDA/EMA-approved status, along with those already experimented at the clinical level and potential promising candidates.
Current medicinal chemistry 29 (3), pp. 411–452
Recombinant proteins, pharmaceutical enzymes, anticancer biologics, fibrinolytic therapy, cancer en-zymatic starvation, biopharmaceuticals, COLLAGENASE CLOSTRIDIUM-HISTOLYTICUM, TRANSMEMBRANE CONDUCTANCE REGULATOR, FIBRINOLYTIC ENZYME NATTOKINASE, TISSUE-PLASMINOGEN-ACTIVATOR, LACTASE-PHLORHIZIN HYDROLASE, RECOMBINANT HUMAN DNASE, L-ASPARAGINASE ACTIVITY, VEGETABLE CHEESE NATTO, METHIONINE GAMMA-LYASE, PHASE-III TRIAL
Raboni Samanta, Bettati Stefano, Gabellieri Edi, Cioni Patrizia
ID: 463965
Year: 2022
Type: Articolo in rivista
Creation: 2022-02-14 09:14:24.000
Last update: 2022-11-29 11:47:30.000
CNR institutes
External IDs
CNR OAI-PMH: oai:it.cnr:prodotti:463965
DOI: 10.2174/0929867328666210713094722
ISI Web of Science (WOS): 000740838200003