Jones Seminar: Breaking the Pattern—Building Better Biotherapies Through Molecular Stealth Technology

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Meeting ID: 925 7752 0440
Passcode: 386003

Protein therapeutics have proven to be a disruptive technology that is transforming modern medicine at a breakneck pace. These macromolecular drugs are, in effect, nanoscale machines with unparalleled capacity to interface with and selectively modulate biological systems. Proteins’ exquisite functionalities, combined with their inherently designable nature, have positioned them as premier scaffolds for drug development. However, their biological origins also impart unique risks for therapeutic applications. For example, the human immune system is a highly honed pattern recognition and defense network that can inadvertently target protein drugs, and ensuing antidrug immune responses can result in complications such as drug neutralization, deposition of toxic immune complexes, and allergic reactions ranging from mild irritation to life-threatening anaphylaxis.

This talk will present the collaborative development of molecular engineering technologies designed to render protein therapies invisible to the human immune system. These “Stealth Biologics®” offer the promise of improved safety profiles and enhanced therapeutic efficacy. As a case study, we examine lysostaphin, a powerful bactericidal enzyme that represents a next-generation therapy for multidrug-resistant Staphylococcus aureus infections. By precision re-engineering of molecular patterns surveilled by the human immune system, we have created a “deimmunized” lysostaphin that evades the antidrug immune response and can be safely re-dosed to cure recurrent and treatment-refractory infections in preclinical models.

About the Speaker(s)

Karl Griswold
Associate Professor of Engineering, Dartmouth

Dr. Karl Griswold is an associate professor at Thayer School of Engineering at Dartmouth. His research has resulted in the development of innovative high-throughput screens for evolutionary protein engineering, new strategies for protein deimmunization, enhanced protein expression systems, and powerful antibacterial agents to treat drug-resistant infections. At Texas State University, he studied as a DOW Chemical Foundation Scholar and graduated summa cum laude with a BS in chemistry. He received his PhD from the University of Texas at Austin in 2005 and completed a postdoctoral fellowship with Professor George Georgiou before joining the Dartmouth faculty in 2007. Dr. Griswold’s honors include an “Award in Translational Biomedical Engineering” from the Coulter Foundation, a “Granite State Technology Innovation Award” from the NHIRC, and a “Teacher of the Year” award from Thayer School. He has coauthored more than 60 peer-reviewed papers and is an inventor on 6 issued US patents, one foreign patent, and he has numerous US and foreign patents pending. His collaborative research has inspired the spinoff of several affiliated biotech startups that employ proprietary protein design and engineering platforms to create the next generation of safer and more effective biotherapies.

Contact

For more information, contact Megan Oman at megan.e.oman@dartmouth.edu.