Packaging protein drugs as bacterial inclusion bodies for therapeutic applications

Microbial Cell Factories

Commentary

José Luis Corchero¹  Elena García-Fruitós¹  Antonio Villaverde²  Esther Vazquez²  Joaquin Seras-Franzoso²  Ursula Rinas³  Ana Kosoy⁴ 

[1] CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain;Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain;Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain;Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain;Departament de Genètica i de Microbiologia, Universitat Autònoma de Barcelona, Bellaterra, 08193, Barcelona, Spain;CIBER de Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Barcelona, Spain;Institute of Technical Chemistry-Life Science, Leibniz University of Hannover, 30167, Hannover, Germany;Helmholtz Centre for Infection Research, Inhoffenstraße 7, D-38124, Braunschweig, Germany;Janus Development SL, Parc Científic Barcelona, Torre R, Baldiri Reixach 4, 08028, Barcelona, Spain;

关键词: Leukemia Inhibitory Factor;    Dihydrofolate Reductase;    Protein Drug;    Protein Delivery;    Recombinant Bacterium;   

DOI  :  10.1186/1475-2859-11-76

 received in 2012-05-30, accepted in 2012-05-31,  发布年份 2012

来源: Springer

【 摘 要 】

A growing number of insights on the biology of bacterial inclusion bodies (IBs) have revealed intriguing utilities of these protein particles. Since they combine mechanical stability and protein functionality, IBs have been already exploited in biocatalysis and explored for bottom-up topographical modification in tissue engineering. Being fully biocompatible and with tuneable bio-physical properties, IBs are currently emerging as agents for protein delivery into mammalian cells in protein-replacement cell therapies. So far, IBs formed by chaperones (heat shock protein 70, Hsp70), enzymes (catalase and dihydrofolate reductase), grow factors (leukemia inhibitory factor, LIF) and structural proteins (the cytoskeleton keratin 14) have been shown to rescue exposed cells from a spectrum of stresses and restore cell functions in absence of cytotoxicity. The natural penetrability of IBs into mammalian cells (reaching both cytoplasm and nucleus) empowers them as an unexpected platform for the controlled delivery of essentially any therapeutic polypeptide. Production of protein drugs by biopharma has been traditionally challenged by IB formation. However, a time might have arrived in which recombinant bacteria are to be engineered for the controlled packaging of therapeutic proteins as nanoparticulate materials (nanopills), for their extra- or intra-cellular release in medicine and cosmetics.

【 授权许可】

CC BY   
© Villaverde et al.; licensee BioMed Central Ltd. 2012