The formylglycine generating-enzyme (FGE) recognizes and acts specifically on a pentapeptide (CXPXR), oxidizing the cysteine to an unusual aldehyde bearing formylglycine residue (fGly). This conversion to fGly is possible when the sequence is inserted into recombinant proteins. The small FGE target sequence, termed the "aldehyde tag", anchors the Redwood Bioscience technology that can generate homogenous, enhanced biotherapeutics. This platform provides the site specificity and chemical flexibility needed to generate useful post translational modifications on virtually any protein. This ability o affix novel chemical functionalities to a biological entity of interest is an immensely powerful platform for the development and optimization of new therapeutics. As applications of this technology are explored it will be advantageous to have flexibility in the consensus sequence recognized by FGE, so as to permit the modification of as many protein targets as possible, ideally on sites that exist already in their endogenous sequences. A panel of FGE enzyme/tag pairs would be an incredibly powerful platform and generate valuable intellectual property. The new tag sequences will be designed to minimize perturbation of the protein sequence and maximize FGE specific activity, thereby enabling optimized conjugation. This new tag technology will generate bioconjugates with minimal antigenicity and enhanced pharmacokinetics. Towards this end, Redwood Bioscience will embark on a research program using a directed evolution approach with yeast cell surface protein display to generate FGE variants that recognize unique and novel substrates.

Public Health Relevance

Redwood Bioscience's aldehyde tag technology can generate novel, modified recombinant therapeutic proteins. Expanding the technology platform with novel enzymes that recognize unique substrates is an essential component to Redwood Bioscience's business strategy and will lead to the generation of best in class biologics.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Small Business Innovation Research Grants (SBIR) - Phase I (R43)
Project #
1R43GM110797-01
Application #
8709882
Study Section
Special Emphasis Panel (ZRG1-IMST-L (11))
Program Officer
Gerratana, Barbara
Project Start
2014-09-17
Project End
2015-03-16
Budget Start
2014-09-17
Budget End
2015-03-16
Support Year
1
Fiscal Year
2014
Total Cost
$136,275
Indirect Cost
Name
Redwood Bioscience, Inc.
Department
Type
DUNS #
829101331
City
Burlingame
State
CA
Country
United States
Zip Code
94010