Cambridge Healthtech Institute’s Inaugural
Vector Design and Development for Gene and Cell Therapies
Engineering Safer and More Efficacious Vectors
January 20-21, 2020
Part of the Cell & Gene Therapies pipeline
The recent success in gene and cell therapies has necessitated a resurgence in vector engineering. Research and development efforts focusing on vectors to combine low genotoxicity and immunogenicity with efficient delivery have shown promise. However,
numerous delivery challenges must be overcome, including developing techniques to evade preexisting immunity to ensure more efficient transduction of therapeutically relevant cell types, to target delivery, and to ensure genomic maintenance. Fortunately,
vector design and development efforts are overcoming these barriers and demonstrating clinical successes. Cambridge Healthtech Institute’s Inaugural Vector Design and Development for Gene and Cell Therapies conference convenes molecular biologists,
cell-line developers, process developers, vector engineers, material scientists, synthetic biologists, biochemists, geneticists, immunologists, and virologists from biotech and pharma companies, along with clinicians who are driving the advancement
of gene and cell therapies into the clinic.
Final Agenda
SUNDAY, JANUARY 19
4:00 - 6:00 pm Pre-Conference Registration
(Sapphire West Foyer)
MONDAY, JANUARY 20
7:00 am Registration (Sapphire West Foyer) and Morning Coffee
(Sapphire West & Aqua West Foyer)
9:00 Organizer’s Welcome Remarks
Mary Ann Brown, Executive Director, Conferences & Team Lead, PepTalk, Cambridge Healthtech Institute
9:05 Chairperson’s Opening Remarks
Christopher Tipper, PhD, Vice President of Discovery, Touchdown Therapeutics
KEYNOTE PRESENTATION
9:10 Adeno-Associated Virus-Based in vivo Gene Therapy: Capsid Discovery, Therapeutic Payload Design, and Product Characterization
Guangping Gao, PhD, Co-Director, Li Weibo Institute for Rare Diseases Research; Director, Horae Gene Therapy Center and Viral Vector Core; Professor,
Microbiology and Physiological Systems, University of Massachusetts Medical School
Since the first proof-of-concept human application in the early 90’s, the field of Gene Therapy has now entered a stage of unprecedented revolution for clinical translation and commercialization. The progress of human gene therapy has been primarily
driven by vector platform technologies. This presentation will focus on AAV in vivo gene therapy, showcasing capsid discovery and engineering, therapeutic gene expression cassette design and optimization, and preclinical
and clinical evaluations.
9:50 The Development of Recombinant Adeno-Associated Virus/Human Bocavirus Vector Production System
Ziying
Yan, PhD, Research Associate Professor, Department of Anatomy and Cell Biology, The University of Iowa
Recombinant adeno-associated virus vector (rAAV) has low tropism for airways, while Human bocavirus 1 (HBoV1) naturally infects the human respiratory tract. Cross-genera packaging of the rAAV2 genome into the HBoV1 capsid created a hybrid parvoviral vector
rAAV2/HBoV1, which is highly tropic for human airways with an increased packaging capacity of up to 5.8 kb. Understanding the transcriptions of HBoV1 proteins facilitated the development of an efficient rAAV2/HBoV1 production system.
10:20 Networking Coffee Break (Sapphire West & Aqua West Foyer)
10:45 Multiplex and Clonal Assessment of Production Yield of in silico Designed AncAAVs
Christopher Tipper, PhD, Vice President of Discovery, Touchdown Therapeutics
DNA barcoding and terabyte-depth NGS have enabled the ability to track and contrast the basic behavior of multiple AAV capsids in a single experiment. Our rationally designed libraries, combined with the multiparametric data generated from our NGS process,
drive us to develop tools that allow us to discover optimal vectors for patient and industry issues, such as targeting and manufacturability. Recent results from our platform around manufacturability will be discussed.
11:15 Strategies for Engineering Adeno-Associated Virus Capsids with Novel Properties
Andrew Mercer, PhD, Principal Scientist, Gene Transfer Technologies, REGENXBIO
Recombinant Adeno-associated virus (rAAV) has proven to be a safe and efficacious option for gene therapy. Despite success in gene transfer in numerous animal models, clinical trials, and more recently in approved therapeutics, none of the currently described
rAAV serotypes display tropism and infectivity for all possible applications. To overcome these limitations, we are interrogating AAV capsids from nature, attempting rational engineering based on structure-function relationships, and using directed
evolution to create the next generation of rAAV vectors.
11:45 High-Throughput Screening of Adenovirus Infectivity for Accelerated Development
Annicka Evans, PhD, Scientist I, Analytical Development, Gene Therapy, Biogen
Adenovirus (Ad) is commonly used as a helper to produce Adeno-associated Virus (AAV)-based vectors for gene therapy. Throughout optimization of upstream and downstream processes associated with Ad-dependent AAV production, large numbers of samples will
need to be tested for Ad presence and infectivity. Here we will present and discuss our screening method that allows for higher sample throughput and analytical efficiency than gold standard methods.
12:15 pm PANEL DISCUSSION: rAAVs
Moderator: Christopher Tipper, PhD, Vice President of Discovery, Touchdown Therapeutics
Panelists: Speakers of the Session
12:45 Session Break
12:55 LUNCHEON PRESENTATION: Considerations in the Use of Analytical Ultracentrifugation for Characterization of AAV Gene Delivery Vectors
Christopher Sucato, PhD, Associate Director, Biophsical Characterization, Charles River
Analytical Ultracentrifugation (AUC) in the biopharmaceutical industry has traditionally been employed in the analysis of aggregation and higher order structure in protein drug products. More recently, gene delivery vectors have opened new avenues for
AUC-based characterization and QC lot release methodologies. We discuss here the parameters of an AUC method which conform to the objectives of an ICH/cGMP validation, and suggest gap-bridging strategies to maintain a high-quality AUC platform for
use in AAV programs.
2:00 Chairperson’s Remarks
Douglas Jolly, PhD, Executive Vice President, Research & Pharmaceutical Development, Tocagen, Inc.
2:05 Dual AAV Vectors for Inner Ear Delivery of Large Genes
Tyler Gibson, PhD, Scientist II, Decibel Therapeutics
Genetic causes of hearing loss offer an ideal indication for gene therapy. However, the inner ear has a disproportionately high number of large genes that exceed the 4.7 kb carrying capacity of standard adeno-associated viruses (AAV). To deliver
large genes to the inner ear we are using a dual vector approach. Here we demonstrate recombination of two halves of a gene in vitro, ex vivo, and in the inner ear.
2:35 Design Considerations and Testing of Proposed Solutions for a Retroviral Replicating Vector, Toca 511, as an Anticancer Agent in Humans
Douglas Jolly, PhD, Executive Vice President, Research & Pharmaceutical Development, Tocagen, Inc.
Features in a vector designed for anti-cancer activity are partly universal and partly mechanism-specific. Universal features include the use of amplification mechanisms. Toca 511 amplifies its effect by selectively replicating in tumors without significant
inflammation then starting an anti-tumor immune response by administration of well-tolerated small molecule drug as a “trigger” for induction of anti-tumor immunity. In animal models and clinical trials this treatment leads to durable
complete responses and extended survival.
3:05 Find Your Table and Meet Your BuzZ Session Moderator
3:15 BuzZ Sessions with Refreshments
Join your peers and colleagues for interactive roundtable discussions.
Click here for more details
4:30 A Nuclear Genetic Sensor to Measure and Optimize Delivery of Non-Viral DNA into Human Cells
Karmella Haynes, PhD, Assistant Professor, Wallace H. Coulter Department of Biomedical Engineering, Emory University
The small fraction of DNA that reaches the nucleus during non-viral gene delivery is often silenced by mechanisms that are not well understood. Viral transduction is a robust alternative, but has critical limitations, such as cargo size, and side effects,
such as immunogenicity. We developed a genetically encoded sensor to track the fate of unlabeled non-viral DNA in live cells and to support efficient screening for interventions to improve gene delivery.
5:00 Development of Pediatric Gene Therapy Using Nuclease-Free Genomic Editing Technology, GeneRide
Jing
Liao, PhD, Associate Director, Discovery Biology, LogicBio Therapeutics
GeneRide is a promoterless, nuclease-free genome editing technology. Combined with highly liver-tropic AAV vectors, GeneRide harnesses the natural process of homologous recombination to integrate the therapeutic gene site specifically into the
Albumin (Alb) locus in a non-disruptive manner. Following GeneRide treatment, expression of the therapeutic gene is linked to that of Albumin via a 2A peptide and can be applied to
treat the pediatric disease.
5:30 Bioresponsive Liposomes – Modulating the Trigger to Improve Site-Specific Delivery
Francis Szoka, PhD, Professor of Bioengineering, Therapeutic Sciences and Pharmaceutical Chemistry, University of California, San Francisco
Four decades since the original publications of pH-triggered liposomes, improved chemistries and a much better understanding of the cell biology of endocytosis/phagocytosis have provided components that can be used for the intracellular delivery of macromolecules.
I’ll describe modified lipids that can be incorporated into liposomes and that are activated by changes in pH, redox potential, or phosphatase activity during the delivery phase to enable intracellular content delivery.
6:00 - 7:15 Welcome Reception in the Exhibit Hall with Poster Viewing
(Sapphire Ballroom)
7:15 Close of Day
TUESDAY, JANUARY 21
8:15 am Registration (Sapphire West Foyer) and Morning Coffee (Sapphire West & Aqua West Foyer)
8:45 Chairperson’s Remarks
Peter Yingxiao Wang, PhD, Professor, Bioengineering, Institute of Engineering in Medicine, University of California, San Diego
8:50 Precision Engineering to Advance Adoptive T Cell Therapies
Justin Eyquem, PhD, Principal Investigator, Department of Microbiology and Immunology, University of California San Francisco
We showed that targeting a CAR transgene into the TRAC locus improves the safety, the manufacturing, and the performance of CAR T cells, defining it as an optimal landing pad for adoptive T cell therapy. I will discuss our latest developments using the
TRAC platform, including scaling up the TRAC-CAR T cells clinical manufacturing.
9:20 Engineering Genetic Circuits for Controllable CAR T Immunotherapy
Peter Yingxiao Wang, PhD, Professor, Bioengineering, Institute of Engineering in Medicine, University of California, San Diego
Cell-based immunotherapy is a paradigm-shifting therapeutic approach to treatment. However, life-threatening non-specificity and off-target activity against normal, non-malignant cells, as well as cytokine release syndrome, are major problems. To mitigate
these, we genetically engineered immune cells to allow precise control of these engineered cells against target tumors.
9:50 Coffee Break in the Exhibit Hall with Poster Viewing (Sapphire Ballroom)
11:00 mRNA Reprogramming for cGMP iPSC Generation
Jiwu
Wang, PhD, President and CEO, Allele Biotech
iPSC-based cell therapy has a very promising future. In order to achieve its full potential, reprogramming must be safe, proficient, and compliant with cGMP production standards. mRNA-based cell fate manipulation is a highly efficient, footprint-free
method for both iPSC reprogramming and differentiation. Our process allows for precise stoichiometric control of factors in a controlled environment ensuring the processes are repeatable, scalable, safe, effective, and USFDA cGMP Compliant.
11:30 PANEL DISCUSSION: Current Strategies and Emerging Progress for Cell & Gene Therapies
Cell and gene therapies have emerged as promising therapeutic tools to target a variety of disease. However, there are also well-established biotherapeutics that have delivered therapeutic results, including antibodies, recombinant proteins, and antibody-drug
conjugates. Panelists will discuss the current and emerging landscape for these therapies. Ultimately, the patient is the winner.
Moderator:
Peter Yingxiao Wang, PhD, Professor, Bioengineering, Institute of Engineering in Medicine, University of California, San Diego
Panelists:
Justin Eyquem, PhD, Principal Investigator, Department of Microbiology and Immunology, University of California San Francisco
Douglas Jolly, PhD, Executive Vice President, Research & Pharmaceutical Development, Tocagen, Inc.
Jiwu Wang, PhD, President and CEO, Allele Biotech
12:00 pm Close of Vector Design and Development for Gene and Cell Therapies Conference