Portable Fluidic Platform For Rapid Cell-Free Production of Protein Biologics

摘要

A portable fluidic platform for rapid and flexible end-to-end production of recombinant protein biologics includes a bioreactor system hosting stable and robust cell-free translation systems that is fluidically integrated with modular protein separation functionalities (e.g., size exclusion, ion exchange or affinity chromatography systems) for purification of the cell-free expressed product and which are configurable for process-specific isolation of different proteins, as well as for formulation. The bioreactor utilizes lysates from engineered eukaryotic (e.g., yeast) or prokaryotic (e.g., bacterial) strains that contain factors for protein folding and posttranslational modifications. Combination of various purification modules on the same fluidic platform allows flexibility of re-routing for purification of different proteins depending on specific target requirements. Protein synthesis and purification modules are integrated into self-contained disposable fluidic cartridge that eliminates cross-contamination between runs. The platform allows for flexible production of protein biologics within 24 hours (from DNA to purified product).

主权项

1. A portable, modular platform for cell-free production, purification and formulation of a protein, wherein the platform comprises:
a loading module for loading one or more reaction reagents to a reactor module; a reactor module comprising at least one of prokaryotic and eukaryotic cell lysate mixtures, wherein said reactor module receives the one or more reaction agents from the loading module, and wherein said reactor module facilitates production of a target protein via a process selected from: (i) continuous exchange cell-free (CECF) or (ii) batch protein synthesis; a chromatography module for separating the target protein from the lysate mixtures; and a finishing module for polishing and formulation of the target protein; wherein the production, separation and formulation of the target protein are completed within a period of 24 hours.