Cambridge Healthtech Instituteでの初開催
- 5:00 pm Main Conference Registration1:00 pm
Recommended Pre-Conference Short Course2:00 pm
SC2: Introduction to Lipid Nanoparticle Characterization and Formulation
*Separate registration required. See short courses page for details.
Dessert Break in the Exhibit Hall with Poster Viewing1:40 pm
INNOVATING RNA THERAPEUTICS
Circular RNAs: Unexpected Outputs of Many Protein-Coding Genes
Circular RNAs are widely generated across eukaryotic genomes. In fact, for some genes, the abundance of the circular RNA exceeds that of the associated linear mRNA by >10-fold. We are developing methods to identify/characterize circular RNAs as well as understand how the spliceosome selects exons for backsplicing. By characterizing these mechanisms in detail and identifying the functions of mature circular RNAs, we aim to reveal novel therapeutic targets and modalities.
Approaches to the Synthesis and Study of Circular RNAs
Circular RNAs (circRNAs) are a novel class of RNAs distinguished by their covalently-closed topology. There are several challenges to working with circular RNAs including their low abundance NA, their lack of a unique feature, and their sequence similarity to linear RNAs. In this talk, we will describe our approaches to synthesize and purify circRNAs that enable their functional investigations and development into effective therapies.
Sponsored Presentation (Opportunity Available)3:20 pm
Refreshment Break in the Exhibit Hall with Poster Viewing3:50 pm
Synthetic Circular RNA as a New Therapeutic Modality
Orna has developed a highly efficient circularization process for generating large quantities of purified circular RNA (oRNA). We demonstrate, in the absence of modified nucleotides, that oRNA is immunoquiescent via in vitro and in vivo assessment. We present case studies using novel ionizable lipids for the generation of lipid nanoparticles to systemically deliver oRNA therapies for oncology (in situ CAR) and protein replacement.
GlycoRNAs: Building a Bridge between RNA Biology and the Cell Surface
Glycans modify lipids and proteins to mediate inter- and intramolecular interactions across all domains of life. RNA is not traditionally thought to be a major target of glycosylation. Here, we challenge this view with evidence that mammals use RNA as a third scaffold for glycosylation. RNA-glycan conjugates, or glycoRNAs are present in multiple cell types and tissues. Analysis of living cells revealed that the majority of glycoRNAs were present on the cell surface and can interact with members of the Siglec receptor family. New chemical tools and insights into the molecular nature of glycoRNAs will be presented.
Small Circular mRNA Vaccines
Antigen-encoding small circRNA vaccines are highly stable and produce concatemeric antigens, resulting in robust and long-lasting adaptive immunity. Relative to several modified mRNAs, circRNA vaccines elicited up to 10-fold antigen-specific T cells in mice with superior safety. circRNA vaccines are widely applicable for tumor and viral (neo)antigens to elicit CD8+/CD4+ T cell responses in young or immunosenescent-aged mice. Combining circRNA vaccines with immune checkpoint blockade (ICB) reduced tumor immunosuppression and eradicated multiple types of murine tumors, including ICB-resistant BrafV600E melanoma. Moreover, pulmonary circRNA vaccines protected mice from influenza challenge. Overall, small circRNA vaccines are promising for versatile applications.
Close of Day6:00 pm
Dinner Short Course Registration6:00 pm
Recommended Dinner Short Course6:30 pm
SC5: Introduction to Gene Therapy Product Manufacturing and Analytics
*Separate registration required. See short courses page for details.
Registration and Morning Coffee7:30 am
BIOANALYTICS AND BIOMARKERS
Isotyping Anti-PEG Antibody Responses to mRNA Therapeutics
Lipid nanoparticles for mRNA vaccines and therapeutics are coated with polyethylene glycol (PEG) to aid in delivery of the mRNA. However, it is widely reported that a high percentage of humans have pre-existing antibodies to PEG. To better understand how pre-existing or treatment boosted anti-PEG antibodies impact delivery of the mRNA, a suite of assays were developed to isotype the anti-PEG antibody response.
Characterization of Immune Response to mRNA-1230 (Influenza, RSV, and SARS-CoV-2) Vaccine Candidate: A Case Study
Moderna has launched a respiratory combination vaccine program, mRNA-1230, to target three of the most significant viruses causing respiratory disease in older adults: the SARS-CoV-2 virus, influenza virus, and respiratory syncytial virus (RSV). This case study describes clinical assays developed to characterize the immune responses to various strains of the three viruses with a focus on the qualification strategy and results.
Model-Informed Development of RNA Medicines
The role of pharmacometrics or modeling and simulation in the development of siRNA therapeutics and mRNA vaccines will be presented. The session will include the following topics:
- Translational modeling approaches for siRNA and mRNA therapeutics
- Modeling and simulation approaches for Phase III dose selection of siRNA therapeutics and mRNA vaccines
- Dose selection for special cases-- dose modeling for mRNA cancer vaccine and pediatric vaccine dose selection?
Coffee Break in the Exhibit Hall with Poster Viewing10:30 am
Transition to Plenary Keynote Session11:10 am
PLENARY KEYNOTE SESSION
Advancing Innovative Biologics Modalities from Research to Clinical Application - Novel Platforms, Automation, and Computation
Addressing disease biology in the clinic with protein therapeutics has become increasingly complex. Turning to innovative and novel scaffolds offers opportunities to tailor therapeutics not previously possible due to advances in host cell engineering and protein design approaches. Designing and developing these modalities requires a next-generation approach as we exploit increased potential design space and also growing data sources to leverage as we invent the next wave of therapeutics.
YOUNG SCIENTIST KEYNOTE
Engineering Prime Editor Proteins for Therapeutic Applications
Precision gene editing technologies have the potential to address a wide range of genetic diseases. Prime Editing is a recently developed “search-and-replace” gene editing approach that can precisely perform a wide variety of DNA sequence edits at programmed target sites in human genomes without requiring double-strand DNA breaks or donor DNA templates. I will describe advances to prime editing technology that improve its efficiency, specificity, and capabilities for therapeutic applications.
Session Break1:00 pm
Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own1:10 pm
Interactive Discussions are informal, moderated discussions, allowing participants to exchange ideas and experiences and develop future collaborations around a focused topic. Each discussion will be led by a facilitator who keeps the discussion on track and the group engaged. To get the most out of this format, please come prepared to share examples from your work, be a part of a collective, problem-solving session, and participate in active idea sharing. Please visit the Interactive Discussions page on the conference website for a complete listing of topics and descriptions.
TABLE 11: Critical Reagent Qualification for LNP Encapsulated mRNA Therapeutics - IN-PERSON ONLY
- Assay platforms for PK/PD, BioD, and immunogenicity
- Challenges in reagent identification and qualification
- Life-cycle maintenance for stability
- Qualification and bridging for new labeling, processing, and manufacturing
- Planning ahead and best practices for critical reagent management
APPLICATIONS OF RNA MODIFICATION
The SMRTs Way to Fix the Heart (Specific Modified mRNA Translational System)
Chemotherapy leads to loss of cardiomyocytes and leads to heart failure. Therefore, there is a need for therapeutics that can protect cardiomyocytes from cardiotoxic agents. Recently, modified mRNA (modRNA) has emerged as a promising technology for cardiac therapeutics. Using modRNA design, CRISPR technology, and positively charged lipid nanoparticles, we created a cardiomyocytes-specific modRNA translational system that translates exclusively in cardiomyocytes and protects them within minutes after intravenous (IV) injection.
Sponsored Presentation (Opportunity Available)4:20 pm
Ice Cream Break in the Exhibit Hall with Poster Viewing4:35 pm
PEGS BOSTON COMMON: SPEED NETWORKING
How Many New Contacts Can you Make? - IN-PERSON ONLY
Bring yourself, your business cards or e-cards, and be prepared to share and summarize the key elements of your research in a minute. PEGS-Boston will provide a location, timer, and fellow attendees to facilitate the introductions.
TARGETED RNA DELIVERY
Synthetic Biodegradable Lipids for Organ and Cell Selective Delivery
LNPs represent the most advanced nonviral nanoparticle delivery systems that have been extensively investigated for nucleic acid delivery. Here I will discuss the design and development of combinatorial synthetic bioreducible and biodegradable lipid nanoparticles (LNPs) with distinct chemical structures and properties for in vitro and in vivo intracellular mRNA delivery. I will discuss the utilization of a library screening strategy to identify optimal LNPs for organ and cell targeted mRNA delivery and showcase the applications of the optimized LNPs in cell engineering and genome editing.
Targeted siRNA Nanomedicine for Hepatic and Renal Fibrosis
A novel siRNA nanomedicine specific to connective tissue growth factor (CTGF), an important regulator of fibrosis in both hepatic and renal cells, is developed. Nanomedicine is further targeted to asialoglycoprotein receptors on hepatocytes and renal tubular epithelial cells by surface modification with galactosamine ligand, to enhance the cell uptake. On animals this innovative construct showed long circulation time and high accumulation in hepatic and renal tissues, making it a promising mRNA therapeutic for liver and kidney fibrosis.
Combinatorial Design of Lipid Nanoparticles for mRNA-Mediated Pulmonary Genome Editing
We describe a high-throughput chemical approach for the synthesis and screening of lipid nanoparticles (LNPs) composed of 720 unique ionizable lipids, which identified key structural features for biodegradable ionizable lipids. The intratracheal administration of lead mRNA-LNP formulations efficiently delivers genes to cells in pulmonary epithelial tissues. The gene editing capabilities were validated using a Cre and CRISPR-Cas9 model, providing a new gateway to treat pulmonary genetic disorders.
Networking Reception in the Exhibit Hall with Poster Viewing6:40 pm
PEGS BOSTON COMMON: WOMEN IN SCIENCE MEET UP
Women In Science Meet Up - IN-PERSON ONLY
The Women in Science Meet Up celebrates women trailblazers who are setting their own course in science. We invite women and men to come celebrate the successes of these women in breaking down barriers and inspiring future generations of female leaders. Come join fellow scientists and share your personal and professional journey.
- Who or What inspires you to explore a career in science?
- What fuels your imagination and spirit when you’re faced with challenges?
- What is your proudest moment?
- What can each of us do to improve things further?
Close of mRNA Therapeutics Conference7:40 pm