Details

Project TitleYeast-Based Intein Platform for Drug Production
Track CodeP150056US02
Websitehttp://www.warf.org/technologies/summary/P150056US02.cmsx
Short DescriptionThe therapeutic and biochemical properties of proteins including antibodies can be enhanced by custom chemical functionalization that enables modifications, such as small molecule drug conjugation, PEGylation and conjugation to nanoparticles. Expressed protein ligation (EPL) is one common approach to chemically modify proteins in a site-specific manner. In EPL, the target protein is expressed as a fusion partner to a non-self-cleaving intein such as Mxe GyrA, which is able to excise itself and join the remaining portions.

These fusion proteins are most often expressed in E. coli bacteria. However, there are many disadvantages to using bacteria for fusion protein production. Drawbacks include protein refolding, instability and high loss (up to 90 percent) of the intein during expression.

Yeast provide a promising alternative to bacterial expression systems, given their eukaryotic nature and quality control mechanisms. To fully realize the advantages of a yeast-based platform, novel inteins must be developed to increase production.\r\n\r\nUW–Madison researchers have engineered non-self-cleaving Mxe GyrA inteins shown to significantly improve the production of fusion proteins from Saccharomyces cerevisiae. The novel inteins were developed through directed evolution, and they enhance fusion protein display (up to 3x) and secretion levels (up to 30x) compared to the wild type intein. The new yeast-based platform provides a robust alternative to bacterial intein expression systems.
AbstractThe Wisconsin Alumni Research Foundation (WARF) is seeking commercial partners interested in developing engineered inteins for improved production of fusion proteins in yeast.
 
Tagsbiotechnology, drug production, intein
 
Posted DateJul 19, 2017 9:22 PM

Advantages

  • Significantly improves fusion protein display and secretion levels
  • Competitive alternative to bacteria-based systems

Potential Applications

  • Target end users include pharmaceutical or biotech partners interested in developing protein biologic drug conjugates
  • Kit for enhancing production of fusion proteins in yeast
  • Research tools

Additional Information

Contact Information

TTO Home Page: http://www.warf.org



Name : Jennifer Gottwald

Title : Director of Licensing

Department : Licensing

Email : jennifer@warf.org

Phone : 608-960-9854

Address : 614 Walnut Street, 13th floor, Madison, WI 53726

Principal Investigator

Name : Cathryn Marshall

Department : Chemical Engineering



Name : Eric Shusta

Department : Chemical Engineering

Intellectual Property

Patent Number : 9,771,412

Patent Title : ENGINEERED INTEIN FOR IMPROVED PRODUCTION OF PROTIEN-INTEIN FUSIONS

Patent Application Date : Oct 29, 2015

Patent Publication Date : May 5, 2016

Patent Issue Date : Sep 26, 2017

Patent Link : http://www.warf.org/documents/ipstatus/P150056US02.PDF