*All times are in EDT
8:20 am Chair’s Opening Remarks
ASSESSING APPROACHES TO DEVELOP MORE TARGETED, LESS IMMUNOGENIC NOVEL CAPSIDS
8:30 am Developing an Optimized Directed Evolution Platform to Engineer Safer, Specific Vectors for Gene Therapy
Synopsis
- Understanding the selective pressures that can be applied (in vitro/in vivo models, animal model types) to improve clinical applicability
- Directed Evolution is not necessarily a standalone method – what other strategies can be incorporated to improve overall capsid optimization?
- Utilizing next generation sequencing and how this data informs engineering models
9:00 am Optimizing AAV Capsids for In Vivo Gene Delivery Using Artificial Intelligence
Synopsis
- Engineered capsids improve the efficiency and tissue specificity of gene delivery relative to natural AAV variants
- Next-gen technologies enable comprehensive mapping of the capsid fitness landscape in NHP models
- Artificial intelligence dramatically accelerates the design of improved capsids for gene delivery
9:30 am Virtual Speed Networking
ADDRESING IMMUNOGENICITY OF AAV BY MODIFYING VECTOR DESIGN
10:30 am Adapting Vector Design to Address Immunogenicity Concerns in Gene Therapy
Synopsis
- Reduction of immunogenic regions in the open reading frame – techniques and fundamentals
- Modifying promoters to decrease immunogenicity while maintaining or increasing protein expression
- Evaluation of modified vector designs for immunogenic response
11:00 am PANEL DISCUSSION: Assessing Capsid Engineering Techniques – Searching for the ‘Perfect’ Capsid
Synopsis
- Discussing different techniques to engineer capsids
- How can we assess which capsids are not only effective but also scalable in manufacturing?
- Will, there ever be a ‘one size fits all’ capsid?
- Highlighting progress in preclinical and clinical trials with optimized AAV capsids
- Can lentiviral capsids be improved in a similar way to AAV – what are the cross-learnings?
12:00 pm Lunch & Networking
INCREASING VECTOR TROPISM TO INCREASE SPECIFICITY & REDUCE TOXICITY
1:30 pm Achieving Cell-Specific Targeting through Capsid Modifications
Synopsis
- Utilizing DNA shuffling to create chimeras of viruses that will more efficiently target cells of interest
- Discussing the advantages of in vivo screening in small and large animals to improve translatability of vectors
- Case Study: Developing a vector to target a specific cell type, and discussing changes unique to the target versus changes for overall vector efficiency
2:00 pm Improving Liver Transduction through AAV Capsid Modifications
Synopsis
- More efficient targeting of specific cells can be achieved through capsid engineering
- Setting up the right model is critical to screen most potent capsids for human application
- Increasing expression in desired targets leads to lower doses required which is key in reducing toxicity in systemic delivery
- Sharing data on novel capsid variants with increased liver tropism
2:30 pm Afternoon Break & Networking
2:35 pm
A HOLISTIC APPROACH TO GENE THERAPY VECTOR DESIGN & DEVELOPMENT
3:00 pm Building a Tailored AAV Vector Platform to Target Ocular Diseases with Greater Efficiency & Reduced Immunogenicity
Synopsis
- Tailoring the AAV vector platform to target specific diseases
- Development of promoters to improve cell-specific targeting
- Modifying cis-regulatory elements to modulate transgene expression and reduce immunogenicity
- Capsid engineering – selecting the right capsid to do the right job
3:30 pm Discovering the Next Generation AAV Vector Through Capsid Engineering & Expression Cassette Optimization
Synopsis
- Novel methods to build AAV capsid libraries for in vivo screening through rational design and directed evolution
- Tissue specific promoter and enhancer engineering to optimize transgene expression