Packaging protein drugs as bacterial inclusion bodies for therapeutic applications.
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.
Institut de Biotecnologia i de Biomedicina, Universitat Autònoma de Barcelona, Bellaterra 08193, Barcelona, Spain. antoni.villaverde@uab.cat
Antonio
A
Villaverde
Elena
E
García-Fruitós
Ursula
U
Rinas
Joaquin
J
Seras-Franzoso
Ana
A
Kosoy
José Luis
JL
Corchero
Esther
E
Vazquez
D001419:Bacteria / Q000378:metabolism; D002374:Catalase / Q000378:metabolism; D016503:Drug Delivery Systems; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D002479:Inclusion Bodies / Q000378:metabolism*; D053547:Keratin-14 / Q000378:metabolism; D053605:Leukemia Inhibitory Factor / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000235:genetics; D013762:Tetrahydrofolate Dehydrogenase / Q000378:metabolism
D018840:HSP70 Heat-Shock Proteins; D053547:Keratin-14; D053605:Leukemia Inhibitory Factor; D011506:Proteins; D011994:Recombinant Proteins; D002374:Catalase; D013762:Tetrahydrofolate Dehydrogenase