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

  • Melissa Kotterman Co-Founder; Vice President, Discovery & Engineering, 4D Molecular Therapeutics

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

  • Nachi Gupta Chief Technology Innovation Officer, Kriya Therapeutics

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

  • Lawrence Tam Group Lead, Vector Engineering, Gyroscope Therapeutics

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

  • Ye Liu Senior Director, Gene Transfer Technology, R&D, REGENXBIO

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

4:00 pm Chair’s closing remarks

  • Robert Kotin Adjunct Professor, University of Massachusetts