Engineering adeno-associated viruses (AAVs) to enhance immune evasion
Project Description
Adeno-associated viruses (AAVs) are promising gene therapy vectors in clinics given their safety profile and relatively high efficiency in delivery. However, natural types of AAVs are limited in use because of the pre-existing neutralization antibodies in patients upon administration. To overcome these limitations, current proposal will focus on using structure-based computational algorithm to engineer AAV capsid sequences with enhanced immune evasion. Specifically, the algorithm will be applied to predict and identify optimal cross-over points in the capsid sequences of AAV natural serotypes with an objective of minimizing structural disruption but maximizing immunological epitope disruption. We aim to create a library of chimeric AAVs that can efficiently bypass the immune system for efficient transduction in targeted cell populations.
Supervisor
ZHU, Bonnie Danqing
Quota
1
Course type
UROP1100
Applicant's Roles
1) Perform thorough literature research and develop an understanding of AAV biology and sequence design;
2) Design the methodology of computational framework for in silico sequence design;
3) Conduct experiments (laboratory and computational) and analyse data, test and optimise the design;
4) Communicate and present research updates weekly and complete lab report.
2) Design the methodology of computational framework for in silico sequence design;
3) Conduct experiments (laboratory and computational) and analyse data, test and optimise the design;
4) Communicate and present research updates weekly and complete lab report.
Applicant's Learning Objectives
• To predict in silico the optimal crossover junctions in natural AAV capsid sequences with maximum epitope disruption and minimum capsid structure disruption.
• To generate a diverse pool of AAVs consisting of chimeric capsid sequences originating from multiple natural serotypes.
• To synthesize and validate designer AAV variants in vitro and in vivo (in fall semester).
• To generate a diverse pool of AAVs consisting of chimeric capsid sequences originating from multiple natural serotypes.
• To synthesize and validate designer AAV variants in vitro and in vivo (in fall semester).
Complexity of the project
Moderate