Recombinant proteins are notorious for their short half-lives and reduced bioavailability. As more novel therapeutic proteins are identified from human genome-sequencing projects, there is an increasing need to formulate protein delivery strategies to prolong the half-life of proteins. Many promising protein therapeutics are abandoned at clinical stages for their inability to sustain therapeutic levels of protein in the body. At times process development costs are prohibitive to justify commercialization. Development of technologies that enhance pharmacokinetics profiles of therapeutic proteins or vaccines will be highly advantageous for many candidate proteins. Indeed technologies have been developed that help increase half-lives of proteins, e.g., polyethylene glycol conjugation or fusion to Fc fragments or albumin. However, at times these technologies inactivate proteins or increase cost of goods and development time lines. LifeSensors has developed ubiquitin-like protein SUMO fusion technology to prolong the half-lives of proteins in plasma. SUMO fusion enhances the level of protein production in eukaryotic and prokaryotic cells. SUMO hydrolase efficiently cleaves the junction between SUMO and its fusion protein to generate desired N-termini of a candidate protein. Thus, the SUMO fusion system can be used to generate a therapeutic protein that contains 19 different N-termini. LifeSensors hypothesizes that the plasma half-life of a protein is regulated by the identity of its N-terminus. In addition, the fusion of an unstable protein to a highly stable structure, such as ubiquitin or SUMO, will prolong the half-life of the protein. Development of a new and simple technology that prolongs plasma half-life of proteins will be a major advance in biopharmaceuticals.
| Butt, Tauseef R; Edavettal, Suzanne C; Hall, John P et al. (2005) SUMO fusion technology for difficult-to-express proteins. Protein Expr Purif 43:1-9 |
