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. 2012 Jun 11:11:76.
doi: 10.1186/1475-2859-11-76.

Packaging protein drugs as bacterial inclusion bodies for therapeutic applications

Antonio Villaverde  1 , Elena García-Fruitós, Ursula Rinas, Joaquin Seras-Franzoso, Ana Kosoy, José Luis Corchero, Esther Vazquez
Affiliations

Packaging protein drugs as bacterial inclusion bodies for therapeutic applications

Antonio Villaverde et al. Microb Cell Fact. .

Abstract

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.

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Figures

Figure 1
Figure 1
A. 40-Section confocal xyz stack of HeLa cells exposed to GFP IBs, showing IB cell penetrability. Cell membrane is labeled in red and the nuclear material is seen in blue. IBs are observed under their natural green fluorescence as discrete particulate entities. B. GFP IBs embedded or crossing the nuclear membrane are shown in two stack versions, in which the cell membrane is either shown (left) or hidden (right) for clarity. Modified from reference [25] (Copyright Wiley-VCH Verlag GmbH & Co, KGaA. Reproduced with permission).
Figure 2
Figure 2
Recombinant bacteria are conventionally exploited to produce soluble proteins for both Biotechnological and Pharmaceutical industries. Alternatively, recombinant bacteria can be observed as protein production-packaging factories whose products are nanostructured proteinaceous entities formed by functional species (IBs). Despite their limitations, IBs show a spectrum of properties that make them appealing as immobilized catalysts and as biocompatible materials in tissue engineering. The revealing of the therapeutic potential of bacterial IBs as nanopills for protein replacement cell therapy expands the opportunities for the development and tailoring of IBs as desired bioproducts with commercial value.
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