MONDAY, APRIL 2 | 2:00 - 5:00 pm

SC4: Diversity-Oriented Platforms for Ligand Discovery

In the last few decades a number of display technologies have emerged to enable de novo selection of novel entities with therapeutic potential. Display technologies, including phage display, mRNA display, aptamers, and DNA-encoded libraries, are broadly used to identify biological or small molecule compounds with desired activity and function. In all of them, the displayed molecule (proteins, peptides or small molecule) are physically linked to the encoding gene which allows their identification following affinity selection of a complex library in a one-pot mixture. These directed evolution platforms are demonstrating how affinity selection and molecular evolution are helping to expand and expedite the drug discovery process. While there is a common theme between the display platforms, each has unique features that determines the design, application and technical challenges.

Three of these platforms - phage display, mRNA display, and DNA Encoded Libraries - will be introduced in this course. The goal is to discuss the principles, proper application, pros and cons, and recent advances for each platform in drug discovery:

• Phage display (Sepideh Afshar/Eli Lilly)
• mRNA display (Sepideh Afshar/Eli Lilly)
• DNA-encoded libraries (Svetlana Belyanskaya/GSK)

Instructors:

Sepideh Afshar, Ph.D., Principal Research Scientist, Department of Protein Engineering, Eli Lilly and Company

Sepideh Afshar is a group leader and principle scientist at Eli Lilly and Co. Sepi has a B.S. in chemical engineering and has received a PhD in Microbiology, Immunology, and Molecular Genetics from UCLA. Her graduate work at Dr. Sherri Morrison’s lab was focused on protein engineering with emphasis on Antibody-Directed Enzyme Prodrug Therapy. Immediately after completion of her graduate work in 2009, she joined Eli Lilly Biotech Center in San Diego. Since then, she has been responsible for establishing new drug discovery platforms that complement the existing discovery practices at Lilly. Her current focus includes protein-protein interaction, oral peptide delivery, and developing peptide-protein fusions which cross the blood brain barrier.

Svetlana Belyanskaya, PhD, Scientific Leader, Encoded Library Technologies, R&D Platform Technology & Science, GSK Boston

Svetlana Belyanskaya is Scientific Leader at Encoded Library Technology (ELT) group at GlaxoSmithKline. Svetlana has been involved in the development of DNA-encoded technology at Praecis Pharmaceutical and significantly contributed in designing and adapting the DNA tagging strategies for DNA- Encoded Libraries. She led biochemistry and affinity based selection effort for several targets, partnered between GSK and Praecis Pharmaceutical. This effort resulted in the discovery of a series of potent and selective inhibitors, one of which is currently undergoing clinical trials. Post GSK acquisition, Svetlana led a team of scientists in the ELT Lead Discovery group and was responsible for ELT selections against multiple targets. Her team discovered multiple target specific small molecules with different MOAs, several of which were the first known small molecule inhibitors for novel targets.