Designing and Manufacturing a New Generation of Biotherapeutics
XpressCF® and XpressCF+® Platforms
Conventional methods for expressing proteins utilize cell lines originating from bacteria, yeast, insects, plants, or mammals. Because these methods require intact, functioning cells, the biochemical and biophysical parameters under which proteins are produced using these methods are inherently limited, often failing to produce many proteins and biologics. Using cell-based expression systems to produce protein variants is also a cumbersome way to enable selection of the best therapeutic candidates.
Our technology is different. Sutro’s technology platform is made possible by the separation, into an extract, of the cellular components required to produce proteins from the process of protein generation itself. The extract includes all the necessary biochemical components for energy production, transcription and translation and can be used to support cell-free biochemical protein synthesis by the addition of the specific DNA sequence for the desired protein. The process produces single proteins at g/L yields in 8-10 hours at any scale
A wide variety of protein products have been produced using Sutro’s platform. These range from small peptides to multimeric complex mammalian proteins such as monoclonal antibodies. Uniquely, production of proteins in our cell free system can be scaled rapidly from sub-1mL scale to manufacturing scale; the platform is effectively a liquid handling solution to protein synthesis. The advantages of such a flexible platform over conventional cell-based expression systems are enormous:
Proteins can be rapidly engineered and optimized by producing many variants in parallel in 96-well plates from DNA libraries
Master Cell Bank
A single master cell bank used for extract generation can provide the manufacturing platform for many different proteins, leading to accelerated development
Produced within Days
Large quantities of a particular protein can be produced within days from first DNA synthesis, allowing pharmacology and safety assessments to be performed during the design and discovery phase of development
Linearly scalable candidate production is assured with predictable performance from bench to GMP production
Surge Protein Production
Extract stockpiling permits flexible and fast deployment of surge protein production in the event of unexpected demand for product
Sutro designs, discovers, characterizes, and manufactures therapeutic proteins for the treatment or prevention of diseases for itself and for its partners using its proprietary XpressCF® platform technologies. Our XpressCF® technology allows us to provide customized manufacture, design and development of therapeutic proteins using cell-free protein synthesis. XpressCF® also enables our non-natural amino acid conjugation technology XpressCF+® and our discovery technology ProteinSAR™.
XpressCF+® allows customized manufacture, design and development of therapeutic proteins that contain an non-natural amino acid in addition to the 20 natural amino acids. Using XpressCF+® to incorporate an non-natural amino acid results in a protein that can be conjugated to one or more chemicals of interest in a site specific manner, enabling homogenous single-species protein-drug conjugates. For example, XpressCF+® is used to make Sutro’s clinical ADC products, STRO-001 and STRO-002, in which a cytotoxin is conjugated to an antibody containing non-natural amino acids.
In addition, Sutro uses ProteinSAR™ to conduct research to identify and characterize the structure, function and the relationship of the therapeutic proteins. Sutro’s advanced technology allows a rapid and deep analysis of structure-function relationship that is not practical with traditional cell-based methods for protein expression.