Current Synthetic and Systems Biology
Open Access
ISSN: 2332-0737
+44-77-2385-9429
ISSN: 2332-0737
+44-77-2385-9429
Christopher D Bahl
University of Washington, USA
Posters-Accepted Abstracts: Curr Synthetic Sys Biol
Naturally occurring disulfiderich miniproteins are often touted as â??natures drugs,â? and are employed by organisms as signaling molecules, antiviral and antimicrobial defense proteins, and toxins. These scaffolds have great potential to succeed under circumstances where antibody based therapies are unsuitable. They are poorly or nonimmunogenic, thermostable, protease resistant, and they can be chemically synthesized. The presence of multiple covalent disulfide crosslinkages confers extreme stability to these proteins, and could be the key to unlocking inhaled, topological, or oral protein drug delivery. However, engineering these proteins into drugs with novel function has been hindered by the limited diversity of naturally existing scaffolds. To circumvent this issue, we have developed a de novo protein design method to custom tailor small, hyperstable affinity reagents against a given target interface by rational design. By utilizing massively parallel, chipbased gene synthesis and yeast cellsurface display, we have created a highthroughput experimental assay. To validate our method, we have successfully produced affinity reagents against a neutralizing epitope of influenza hemagglutinin. Our technology is the first to allow rapid, cost effective generation of highly targeted protein therapeutics with the potential to treat a wide variety of diseases.
Email: cdbahl@uw.edu