Julia Paoli

Mentor:

Mavis Agbandje-McKenna 

College of Medicine 

Major: Microbiology and French 

Minor: N/A

Research Interests: VirologyVaccine development, Cancer treatment. 

Academic Awards: Stamps Scholar 2016-2020, Sones Scholarship 2017, Emerging Scholar 2017-2018, 

Organizations: Honors Ambassadors, University Orchestra, TEDXUF

Volunteer: Dream Team at Shands, Baby Gators, Habitat for Humanity

Hobbies and Interests: Skiing, playing violin, traveling, ballet

Research Description:

Developing Antibody Escape Mutants for AAV3b

In viral-vector gene therapy, viruses are utilized to infect and deliver new genes into target cells. Native viral DNA is removed and replaced with a desired therapeutic gene. Adeno-associated viruses (AAVs) exhibit potential to be used as effective gene therapy vectors. The serotype AAV3b has been shown to specifically target human liver cancer cells. According to the American Cancer Society, more than 700,000 people worldwide are diagnosed with liver cancer each year. Additionally, liver cancer is a leading cause of cancer deaths globally, causing more than 600,000 deaths per year. My project aims to replace the native viral DNA in AAV3b with a gene that triggers cancer cell death, particularly in liver cancer cells.

However, AAV3b’s potential as a vector is limited by the high percentage of the human population, 40-70%, who exhibit pre-existing host immunity against AAVs. In order for AAV3b to be used effectively in gene therapy, the virus needs to escape recognition from patients’ antibodies. Previously, my research mentor, Dr. Agbandje-McKenna, determined the capsid structures of several AAV serotypes using Cryo-EM analysis. Using this information, I will identify where on the AAV3b viral capsid several types of antibodies bind. From there, I will create mutant AAV3b viruses with altered capsid regions that prevent antibodies from binding. Once I have successfully created a mutant that can escape antibody recognition, future studies on using that mutant as a gene therapy vector can proceed.