Recombinant system for ultra-large scale biomanufacturing of therapeutic proteins

DESCRIPTION (provided by applicant): Solazyme, Inc. in collaboration with the City University of New York (CUNY) proposes to develop a novel recombinant protein expression platform by transforming the photosynthetic microalgal species Dunaliella salina. The organism's autotrophic production of nutrients from sunlight and extreme halotolerance will allow new biomanufacturing processes to overcome the limitations on scaling of bioreactor size inherent to conventional recombinant cell culture systems. By enabling production of therapeutic recombinant proteins on an ultra-large scale, the platform will solve critical problems that confront current biomanufacturing techniques, such as the prohibitively high capital costs for new facilities and the difficulty of rapidly expanding production to satisfy unexpected demand. Our approach will particularly benefit manufacturing of health products required in high quantities, including many monoclonal antibodies, therapeutic proteins such as human serum albumin, industrial biopharmaceutical enzymes such as trypsin, and products needed to respond rapidly to emerging highly infectious diseases or bioterror threats. The objectives of the overall project (Phases I and II) are to transform strains of D. salina to express a commercially useful biopharmaceutical protein, create a modular vector system to facilitate rapid development of strains expressing other recombinant proteins, optimize expression levels to create "protein factories", and demonstrate initial scale-up and ease of product purification. These results will serve as the basis for a commercial production process to be licensed to biopharmaceutical companies. Phase I will establish feasibility by demonstrating transformation of D. salina and verifying stable incorporation of a foreign gene into the organism's nuclear chromosomal DNA for the first time. Phase I objectives include vector construction, development of techniques to prepare the cells by permeabilizing their glycoprotein sheath, transformation by electroporation, and verification by RT-PCR and Western Blot analyses. Relevance: Many new protein drugs treating a wide range of serious diseases and conditions (including many cancers, acute blood loss, rheumatoid arthritis, etc.) are now available or under development. The difficulty of manufacturing these protein therapies results in high prices and may lead to supply constraints. The proposed biomanufacturing platform will lower production costs and ensure adequate supply to patients.