Cambridge Healthtech Instituteの初開催

Emerging mRNA Therapeutics
(新興のmRNA医薬)

設計、デリバリー、最適化、適応症

2023年3月13 - 14日、EDT(米国東部標準時)

SARS-CoV-2のパンデミックに対するメッセンジャーRNA(mRNA)ワクチンの成功により、がん、心血管疾患、代謝疾患、希少遺伝性疾患などの治療に対するmRNA追求への関心が高まっています。mRNA医薬品の開発と規制当局の承認までの道のりは、低分子より早くなる可能性があります。しかし、mRNA合成、精製、標的化デリバリー、免疫原性などに関する課題は、広く普及させる前に対処する必要があります。Cambridge Healthtech Instituteの初開催「新興のmRNA医薬」会議では、さまざまな適応症に対する標的療法を開発するための有効な薬剤モダリティとして、mRNAを開発するために行われている取り組みが紹介されます。

3月13日(月)

Main Conference Registration9:15 am

Welcome Remarks by Conference Organizer10:40 am

EMERGING RNA MODALITIES
新興のRNAモダリティ

10:50 am

Chairperson's Opening Remarks

Paloma H. Giangrande, PhD, Vice President, Platform and Discovery Sciences Biology, Wave Life Sciences

10:55 am

The Therapeutic Potential of oRNA

Robert Mabry, PhD, CSO, Orna Therapeutics

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.

11:25 am

Programmable Epigenomic Medicines: A New Class of mRNA Therapeutics

Thomas McCauley, PhD, CSO, Omega Therapeutics, Inc.

Gene regulation, in health and disease, is mediated by the epigenetic modification to tune gene expression in a cell state-specific manner. Omega Therapeutics is developing programmable epigenetic mRNA therapeutics through an innovative platform capable of precisely and durably modifying chromatin state to treat disease. Based on a computationally guided, modular, and engineered approach, our epigenetic medicines can tune-expression one or many targets with high likelihood of translational success.

11:55 am

RNA Activation in Acquired and Genetic Diseases

Nagy Habib, ChM, FRCS, Head of R&D and CMO, MiNA Therapeutics Ltd.

Small activating RNAs (saRNA) are double-stranded 21 nucleotide RNA that either target promoters or enhance genes leading to mRNA upregulation. MTL-CEBPA is an investigative drug that resulted from the conjugation of saRNA CEBPA with NOV 340 liposomes that targets tumor associated macrophages in order to alter favorably the tumor microenvironment. MTL-CEBPA has been administered safely in over 100 patients with advanced cancer and improved clinical outcome in a sub-set of patients when co-administered with TKI or check point inhibitor. 

Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:25 pm

Grand Opening Dessert Break in the Exhibit Hall with Poster Viewing12:55 pm

UNDERSTANDING RNA-DRIVEN CANCER BIOLOGY
RNA主導のがん生物学の理解

1:35 pm

Chairperson's Opening Remarks

Mark Kay, MD, PhD, Dennis Farrey Family Professor of Pediatrics and Genetics, Department of Pediatrics and Genetics, Stanford University

1:40 pm

miRNA-Based Logic Circuits Encoded on Self-Amplifying RNA for Highly Specific Cancer Cell Classification

Ron Weiss, PhD, Professor, Biological Engineering, Massachusetts Institute of Technology

We developed self-amplifying RNA and modified RNA platforms into vectors capable of carrying synthetic circuitry payloads that can provide a variety of desirable dynamics. Utilizing natural and synthetic RNA-binding proteins (RBPs), we constructed a toolbox capable of regulating expression via non-degradative, reversible binding to transcripts expressing therapeutic proteins of interest. We also encoded miRNA target sites on our RNA vectors to provide for highly specific cell type classification. We are using this technology to create next-generation cancer immunotherapy RNA vectors capable of activating therapeutic payloads discriminately in cancer cells.

2:10 pm FEATURED PRESENTATION:

Novel RNAs for Treating Cancer

Mark Kay, MD, PhD, Dennis Farrey Family Professor of Pediatrics and Genetics, Department of Pediatrics and Genetics, Stanford University

I will discuss a miRNA that has long been known to have anti-oncogenic properties and is derived from a long primary transcript, which we recently discovered has a separate tumor suppressor function. The role and anti-oncogenic mechanism by which this long non-coding RNA functions will be discussed. In addition, the therapeutic implications for therapeutic intervention will also be examined.

2:40 pm Making innovation reality: strategies for future manufacturing requirements

Katarina Stenklo, Enterprise Solutions Commercial Activation Leader, Bioprocess, Cytiva

mRNA technology has changed the way therapies are developed. The overall potential of mRNA is clear, with mRNA therapeutics being developed in many research areas. Much of the current equipment used in manufacturing is repurposed from the biotech industry and is designed for much larger scales than needed for mRNA.

 

What are the challenges associated with smaller scales and how can manufacturers prepare for rapid response?

Refreshment Break in the Exhibit Hall with Poster Viewing3:10 pm

PLENARY SESSION
プレナリーセッション

3:50 pm

Plenary Chairperson's Remarks

Dmitry Samarsky, PhD, CTO, Sirnaomics

3:55 pm PLENARY PRESENTATION:

Biological Studies with Thiomorpholino Oligonucleotides

Marvin Caruthers, PhD, Distinguished Professor, University of Colorado

Currently underway are more than 20 biological studies focused on the use of thiomorpholino oligonucleotides (TMOs) as a therapeutic drug for the treatment of various genetic diseases. These collaborations are being carried out with cells in culture and several have progressed to studies in mouse models. Without exception, TMOs are more active than any other analogue tested and, in one case, a TMO is active under conditions where the 2'-MOE analogue is toxic to mice in the same treatment group.

4:25 pm PLENARY PRESENTATION:

Advances in CRISPR Genome Editing for Therapeutics Application

Rubina Parmar, PhD, Vice President, Chemistry & Delivery Sciences, Intellia Therapeutics, Inc.

At Intellia, we are building a full-spectrum genome editing company. We are deploying the industry's broadest and deepest toolbox, including novel editing and delivery solutions, to harness the immense power of CRISPR-based technologies for in vivo and ex vivo therapeutic applications, each with the potential to revolutionize the future of medicine. In this presentation, we will share the advances in the therapeutic application of CRISPR/Cas9 for genome editing.

4:55 pm PLENARY PRESENTATION:

Recent Developments in Oligo Conjugates

Arthur Levin, PhD, CSO, Avidity Biosciences

The promise of oligonucleotide therapeutics is to use Watson-Crick-Franklin base-pairing rules to design drugs directly and rationally based on genomic information. Until recently, that promise has remained elusive because of cell barriers to oligonucleotide uptake. Receptor-mediated uptake through bioconjugation oligonucleotides has changed that. Avidity's AOC technology uses monoclonal antibodies to cell surface proteins that are internalized in order to facilitate the functional delivery of oligonucleotide therapeutics into a broad range of cell and tissue types. 

Welcome Reception in the Exhibit Hall with Poster Viewing5:25 pm

Close of Day6:25 pm

3月14日(火)

Registration and Morning Coffee7:45 am

INNOVATIONS IN mRNA MODIFICATIONS
mRNA修飾におけるイノベーション

8:30 am

Chairperson's Opening Remarks

Robert Mabry, PhD, CSO, Orna Therapeutics

8:35 am

Chemically Modified mocRNAs for Highly Efficient Protein Expression in Mammalian Cells

Xiao Wang, PhD, Assistant Professor, Department of Chemistry, Broad Institute of MIT and Harvard

I will introduce messenger-oligonucleotide conjugated RNAs (mocRNAs) to enable site-specific, robust, and modularized encoding of chemical modifications for highly-efficient and stable protein expression. By directly linking enzymatic and organic synthesis of mRNA, we envision that the mocRNA design will open new avenues to expand the chemical space and translational capacity of RNA-based vectors in basic research and therapeutic applications.

9:05 am

mRNA-Based Cancer Immunotherapies: Encoding Vaccines to Immunomodulatory Proteins

Sushma Gurumurthy, PhD, Director, Oncology Research, Moderna, Inc.

While immunotherapies have demonstrated striking responses in several hard to treat cancers, therapies do not work in all cancers and cures are not seen in all patients. Modified mRNA technology has been successfully applied in the development of vaccines, most recently against SARS-CoV-2 virus in the fight against COVID-19. I will present our application of mRNA therapies to develop novel immune-mediate therapies that activate the ability of the immune system to develop durable anti-tumor immunity with approaches ranging from encoding cancer vaccines against shared and personalized tumor antigens to different immunomodulatory proteins.

9:35 am FEATURED PRESENTATION:

Innovations in mRNA Therapeutics

Drew Weissman, MD, PhD, Roberts Family Professor in Vaccine Research, Department of Infectious Diseases; Director of the Penn Institute for RNA Innovation and Professor, Department of Medicine, University of Pennsylvania

Vaccines prevent 4-5 million deaths a year, making them the principal tool of medical intervention worldwide. Nucleoside-modified mRNA (modmRNA) is responsible for the first 2 FDA-approved vaccines. These vaccines show greater than 90% efficacy and outstanding safety. Vaccines against many pathogens are in development. ModmRNA is also being developed for therapeutic protein delivery and gene therapy. modmRNA will have an enormous potential in the development of new medical therapies.

10:05 amBreakout Discussions

Breakout discussions provide an opportunity to discuss a focused topic with peers from around the world in an open, collegial setting. Select from the list of topics available and join the moderated discussion to share ideas, gain insights, establish collaborations or commiserate about persistent challenges. Please visit Breakout Discussions for a complete listing of topics and descriptions.

IN-PERSON BREAKOUT DISCUSSION:

Developing mRNA Therapeutics

Paloma H. Giangrande, PhD, Vice President, Platform and Discovery Sciences Biology, Wave Life Sciences

Mark Kay, MD, PhD, Dennis Farrey Family Professor of Pediatrics and Genetics, Department of Pediatrics and Genetics, Stanford University

Robert Mabry, PhD, CSO, Orna Therapeutics

Drew Weissman, MD, PhD, Roberts Family Professor in Vaccine Research, Department of Infectious Diseases; Director of the Penn Institute for RNA Innovation and Professor, Department of Medicine, University of Pennsylvania

  • Challenges with mRNA delivery
  • Innovative mRNA modifications
  • Emerging mRNA formats (circular, replicating etc.)
  • Tackling mRNA safety


Coffee Break in the Exhibit Hall with Poster Viewing10:50 am

NEW FORMULATIONS FOR TARGETED DELIVERY
標的化デリバリーの新製剤

11:30 am

Lipid Nanoparticles for Overcoming Biological Barriers to mRNA Delivery 

Michael Mitchell, PhD, Skirkanich Assistant Professor of Innovation, Department of Bioengineering, University of Pennsylvania

The development of nucleic acid therapeutics to both generate therapeutic proteins (via mRNA, pDNA) and silence proteins (via siRNA, miRNA, antisense oligonucleotides (ASOs)) and the development of gene editing technologies (CRISPR-Cas, TALENs, zinc finger nucleases) have opened new opportunities to precisely edit the genome and potentially enable one-time cures of genetic diseases. However, these therapeutics must overcome numerous obstacles to be successful, including rapid in vivo degradation, poor uptake into target cells, required nuclear entry, and potential in vivo toxicity in healthy cells and tissues. In this talk, I will discuss our efforts towards the development of new lipid nanoparticles (LNPs) that enable the delivery of nucleic acid therapeutics to target cells and tissues in vivo. Furthermore, I will describe new therapeutic strategies utilizing these LNPs for (i) mRNA CAR T cell engineering for cancer immunotherapy, and (ii) in utero mRNA delivery for treating disease before birth.

12:00 pm

Therapeutic RNA Delivery Using Protein-Based Nanocapsules

Ekkehard Leberer, PhD, Senior Life Sciences Consultant, ELBIOCON; Advisor, Neuway Pharma

The presentation will introduce NEUWAY's protein-based nanocapsules as a scalable and versatile delivery technology for a broad range of therapeutic RNA applications. The use of these nanocapsules to deliver therapeutic mRNAs across the blood brain barrier will be described. The therapeutic potential of this delivery technology will be illustrated for the mRNA treatment of monogenetic CNS disorders such as metachromatic leukodytrophy (MLD).

Luncheon Presentation (Sponsorship Opportunity Available) or Enjoy Lunch on Your Own12:30 pm

Session Break1:00 pm

OPTIMIZING mRNA THERAPEUTICS
mRNA医薬の最適化

1:40 pm

Chairperson's Remarks

Lior Zangi, PhD, Associate Professor, Department of Medicine, Cardiology and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai

1:45 pm

The SMRTs (Specific Modified mRNA Translational System) Way to Fix the Heart  

Lior Zangi, PhD, Associate Professor, Department of Medicine, Cardiology and Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai

Ischemic heart failure is a leading cause of mortality. This urgent unresolved medical need led scientists to evaluate whether induction of cardiac protection, post cardiac ischemic injury, can attenuate cardiomyocyte (CM) loss. In my talk, I will describe a minimal invasive method, using tail vain I.V injection to deliver therapeutic and protective modRNA directly to CM to attenuate CM cell death and improve the outcome post cardiac ischemic injury.

2:15 pm

Characterizing Immunogenic Side Products of in vitro Transcribed mRNAs

Li Li, PhD, Assistant Professor, RNA Therapeutics Institute, University of Massachusetts Chan Medical School

Current preparations of in vitro transcribed mRNAs contain immunogenic side products. Although these side products can fortuitously act as adjuvants for mRNA vaccines, they continue to impede the development of mRNA therapeutics in other areas, such as protein replacement therapy. We have applied reverse-phase chromatography to fractionate these immunogenic side products, characterized their sequence and structural features, and examined their immunostimulatory effects on dendritic cells.

Refreshment Break in the Exhibit Hall. Last Chance for Poster Viewing2:45 pm

PLENARY SESSION
プレナリーセッション

3:15 pm

Plenary Chairperson's Remarks

Jonathan Watts, PhD, Associate Professor, RNA Therapeutics Institute, University of Massachusetts Chan Medical School

3:20 pm PLENARY PRESENTATION:

Nucleic Acid Delivery Systems for RNA Therapy and Genome Editing

Daniel Anderson, PhD, Professor, Chemical Engineering, Massachusetts Institute of Technology

Here we describe our work developing nanoformulations for RNA therapy and genome editing. Libraries of degradable polymers and lipid-like materials have been synthesized, formulated, and screened for their ability to deliver RNA payloads inside cells. These nanoformulations facilitate in vivo delivery to a range of tissues and can enable targeted gene suppression with siRNA, gene expression with mRNA, or even permanent genetic editing using the CRISPR/Cas9 system.

3:50 pm PLENARY PRESENTATION:

Advances in Chemistry Made RNAi Therapeutics Possible

Mano Manoharan, PhD, Distinguished Scientist & Senior Vice President, Innovation Chemistry, Alnylam Pharmaceuticals

For siRNAs, chemical modifications are necessary to regulate metabolic stability, potency (through effects on the interaction with the Ago2 enzyme and the targeted mRNA strand), and safety (impacted by metabolites and on-target specificity). We have evaluated numerous chemical modifications beyond the standard 2'-O-methyl, 2'-fluoro, and phosphorothioate linkages. These include backbone chiral phosphorothioates, glycol nucleic acids, altriol nucleic acids, gem 2'-deoxy-2'-α-F-2'-β-C-methyl, 5'-morpholino, and amino-oxy click chemistry (AOCC) mediated conjugates. Furthermore, novel spatial architectures like circular siRNAs have also been evaluated. This presentation will summarize how chemistry has made possible the currently exciting world of RNAi therapeutics.

4:20 pm PLENARY PRESENTATION:

Development of mRNA-Based Vaccines

Steve Pascolo, PhD, Senior Scientist, University Hospital of Zurich; Founder & CEO, Miescher Pharma GmbH

The safety and efficacy of mRNA-based vaccines was evidenced during the COVID-19 pandemic: less than one year after the publication of the sequence of SARS-CoV-2, mRNA vaccines against COVID-19 were approved. More mRNA vaccines (against infectious diseases and cancer) are in clinical developments and are expected to be approved in the coming years. New mRNA formats (circular, replicating) and formulations (lipoplexes and polyplexes) are also being tested to further improve mRNA vaccines. I will present the past, present and future of mRNA vaccines.

Close of Conference4:50 pm

* 不測の事態により、事前の予告なしにプログラムが変更される場合があります。

Choose your language
English


OLIGO DISCOVERY AND DELIVERY