Nikki McArthur 

BioE Ph.D. Proposal Presentation 

Time and Date: 1:00 pm on Wednesday, December 7, 2022 

Location: IBB 1128 

Zoom link: https://gatech.zoom.us/j/99770971163?pwd=b1dTUDB6alFXUCtTTXZPVGpiRm1FZz09  

Advisor: Ravi Kane, Ph.D. (Chemical and Biomolecular Engineering) 

Committee Members: 

John Blazeck, Ph.D. (Chemical and Biomolecular Engineering) 

Julie Champion, Ph.D. (Chemical and Biomolecular Engineering) 

Corey Wilson, Ph.D. (Chemical and Biomolecular Engineering) 

Levi Wood, Ph.D (Mechanical Engineering)  

Engineering Multivalent Nanobodies Against Amyloid Proteins and Other Antigens 

Antibodies and antibody-based molecules are effective therapeutics due to their high binding affinity and specificity. Antibody fragments, such as nanobodies, are also successfully used as therapeutics to treat a variety of diseases. Nanobodies are small, single-domain antibodies derived from the variable domain of camelid heavy-chain antibodies. Traditionally, antibodies and antibody fragments that bind to a desired antigen are developed through animal immunization, but techniques for in vitro antibody discovery have been developed. These techniques involve the use of display methods, such as yeast surface display, to screen a library of synthetic antibody fragments against a target antigen. Here, we propose to use in vitro antibody discovery to identify nanobodies that bind to protein targets involved in neurodegenerative and infectious diseases. We will create multivalent versions of the selected nanobodies to improve their avidity and specificity. 

Alzheimer’s disease is a debilitating neurodegenerative disease that affects over six million people in the United States. Most of the drugs available to treat Alzheimer’s disease treat its cognitive symptoms and not the progression of the disease itself. Tau is a protein that misfolds and aggregates into oligomeric and fibrillar structures in Alzheimer’s disease. The accumulation of these aggregates correlates well with Alzheimer’s disease progression, making tau oligomers and fibrils attractive targets for passive immunotherapy. We will develop multivalent nanobodies that target tau oligomers and fibrils and modify them to improve their delivery across the blood-brain barrier. Our multivalent nanobodies will be useful reagents for in vitro characterization of oligomers and fibrils and potential Alzheimer’s disease treatments with the ability to neutralize or clear toxic tau aggregates. 

SARS-CoV-2, the virus that causes COVID-19, is rapidly evolving and new variants of the virus are continually emerging. All antibody treatments for COVID-19 available in the United States are no longer effective against these new variants. Thus, there is a need for new antibody-based therapeutics to target emerging SARS-CoV-2 variants. Using in vitro antibody discovery and multivalency, we will develop multivalent nanobodies that bind to and have the potential to neutralize a selection of SARS-CoV-2 viruses, including new variants of concern.