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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Development of L-Asparaginase Biobetters: Current Research Status and Review of the Desirable Quality Profiles

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Autor(es):
Brumano, Larissa Pereira [1] ; Santos da Silva, Francisco Vitor [1] ; Costa-Silva, Tales Alexandre [1] ; Apolinario, Alexsandra Conceicao [1] ; Picado Madalena Santos, Joao Henrique [1, 2] ; Kleingesinds, Eduardo Krebs [1] ; Monteiro, Gisele [1] ; Rangel-Yagui, Carlota de Oliveira [1] ; Benyahia, Brahim [3] ; Pessoa Junior, Adalberto [1]
Número total de Autores: 10
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Biochem & Pharmaceut Technol, Sao Paulo - Brazil
[2] Univ Aveiro, Aveiro Inst Mat, CICECO, Dept Chem, Aveiro - Portugal
[3] Loughborough Univ, Dept Chem Engn, Loughborough, Leics - England
Número total de Afiliações: 3
Tipo de documento: Artigo de Revisão
Fonte: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY; v. 6, JAN 10 2019.
Citações Web of Science: 1
Resumo

L-Asparaginase (ASNase) is a vital component of the first line treatment of acute lymphoblastic leukemia (ALL), an aggressive type of blood cancer expected to afflict over 53,000 people worldwide by 2020. More recently, ASNase has also been shown to have potential for preventingmetastasis from solid tumors. The ASNase treatment is, however, characterized by a plethora of potential side effects, ranging from immune reactions to severe toxicity. Consequently, in accordance with Quality-by-Design (QbD) principles, ingenious new products tailored to minimize adverse reactions while increasing patient survival have been devised. In the following pages, the reader is invited for a brief discussion on the most recent developments in this field. Firstly, the review presents an outline of the recent improvements on the manufacturing and formulation processes, which can severely influence important aspects of the product quality profile, such as contamination, aggregation and enzymatic activity. Following, the most recent advances in protein engineering applied to the development of biobetter ASNases (i.e., with reduced glutaminase activity, proteolysis resistant and less immunogenic) using techniques such as site-directed mutagenesis, molecular dynamics, PEGylation, PASylation and bioconjugation are discussed. Afterwards, the attention is shifted toward nanomedicine including technologies such as encapsulation and immobilization, which aim at improving ASNase pharmacokinetics. Besides discussing the results of the most innovative and representative academic research, the review provides an overview of the products already available on the market or in the latest stages of development. With this, the review is intended to provide a solid background for the current product development and underpin the discussions on the target quality profile of future ASNase-based pharmaceuticals. (AU)

Processo FAPESP: 17/21819-9 - Otimização e viabilidade econômica do processo de Produção de L-asparaginase recombinante para aplicação farmacêutica
Beneficiário:Larissa Pereira Brumano
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 15/07749-2 - Engenharia de proteínas e comparação de sistemas microbianos de expressão do biofármaco L-asparaginase
Beneficiário:Gisele Monteiro
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 14/10456-4 - Desenvolvimento e caracterização de Polimerossomos de poli (óxido de Etileno-beta-ácido láctico) (PEG-PLA) para veiculação de L-asparaginase recombinante
Beneficiário:Alexsandra Conceição Apolinário
Linha de fomento: Bolsas no Brasil - Doutorado
Processo FAPESP: 13/08617-7 - Produção de L-asparaginase extracelular: da bioprospecção à engenharia de um biofármaco antileucêmico
Beneficiário:Adalberto Pessoa Junior
Linha de fomento: Auxílio à Pesquisa - Temático
Processo FAPESP: 18/03734-9 - Aplicação da filosofia "quality by design" no desenvolvimento do processo produtivo da enzima quimioterápica L-asparaginase
Beneficiário:Francisco Vitor Santos da Silva
Linha de fomento: Bolsas no Brasil - Pós-Doutorado