Cambridge Healthtech Institute's 6th Annual

Oligonucleotide Discovery and Delivery

Optimizing Design, Delivery and Performance

March 30, 2021 ALL TIMES EDT

CHI’s Oligonucleotide Discovery and Delivery conference reveals the latest strategies at the forefront of discovery, chemistry and delivery with in-depth sessions on new chemistries, novel delivery mechanisms and the most important preclinical and clinical advances. Leading oligonucleotide scientists deliver detailed case studies on antisense, RNA, GalNAc, aptamers, conjugates and more – helping you develop the next generation of targeted oligonucleotide therapeutics.

Tuesday, March 30

KEYNOTE SESSION: GALNAC TECHNOLOGY, ANTISENSE AND GENOME EDITING

9:50 am KEYNOTE PRESENTATION:

RNA Targeting with Antisense Oligonucleotides: Present and Future

Richard S. Geary, PhD, Executive Vice President, Drug Development, Ionis Pharmaceuticals

The number and chemical breadth of antisense oligonucleotide (ASO) medicines have rapidly grown in both clinical development and in market approvals. The ASOs currently in development are well balanced between rare and broad diseases and represent significant innovations. Some of the unique aspects associated with single strand ASO chemistry, distribution, cell uptake, clinical pharmacology and safety will be discussed as applied to clinical development examples and overall research progress.

Amanda Haas, Custom Synthesis Product Manager, Horizon Discovery

Oligonucleotide-directed targeting to regulate gene function has enabled genome-wide studies and extended to the hope of targeting any gene. We will discuss the optimization of guide RNA synthesis for CRISPR activation (CRISPRa) which requires substantially longer oligonucleotides.  CRISPRa is the most promising new technology for overexpression, synthesis of CRISPRa guides has allowed rapid evaluation of large gene families.  

 

 

10:30 am KEYNOTE PRESENTATION:

Transforming Medicine: The Power and Promise of Genome Editing for Rare and Genetic Diseases

Laura Sepp-Lorenzino, PhD, CSO, Intellia Therapeutics

At Intellia, we are building a full-spectrum, product-driven biotechnology company focused on our mission of developing and commercializing potentially curative genome editing treatments that can positively transform the lives of people living with severe and life-threatening diseases. On the in vivo side, our systemic lipid nanoparticle or LNP-based delivery system has the potential to unlock treatment of genetic diseases by selectively knocking out disease-causing genes, introducing targeted insertion of a functional gene or both. We are also focused on engineering T cell therapies to provide them with particular enhanced attributes that may enable them to more effectively treat oncological and immunological diseases. Our approach is designed to improve safety and efficacy by engineering cell therapies that are more precise, potent and persistent. The presentation will focus on Intellia’s in vivo platform and pipeline, highlighting the paths to gRNA selection, preclinical pharmacology and the clinic.

10:50 am KEYNOTE PRESENTATION:

GalXC+: Cell-Type Targeted Therapeutic Oligonucleotide Delivery in the CNS

Maire Osborn, PhD, Associate Director, Neuro Discovery, Dicerna Pharmaceuticals

Dicerna’s GalXC RNAi technology provides safe and durable treatment for genetically defined diseases. Recent efforts have focused on GalXC-Plus, a suite of novel RNAi platforms enabling extrahepatic delivery to the central nervous system (CNS), muscle, adipose, and adrenal tissues. The biggest hurdle to developing GalXC-Plus for neurological disease is the need for efficient delivery to specific neural cell types. We will discuss engineering challenges and advances enabling long-lasting, cell-specific gene silencing in the brain, spinal cord, and peripheral nerves of rodents and non-human primates. These discoveries position GalXC-Plus to be effective against a broad range of CNS disorders with no available treatment options.

11:25 am KEYNOTE LIVE PANEL DISCUSSION:

Q&A with Session Speakers

Panel Moderator:
Laura Sepp-Lorenzino, PhD, CSO, Intellia Therapeutics
Panelists:
Mano Manoharan, PhD, Distinguished Scientist & Sr VP Innovation Chem, Innovation Chemistry, Alnylam Pharmaceuticals
Richard S. Geary, PhD, Executive Vice President, Drug Development, Ionis Pharmaceuticals
Amanda Haas, Custom Synthesis Product Manager, Horizon Discovery
Maire Osborn, PhD, Associate Director, Neuro Discovery, Dicerna Pharmaceuticals
11:55 am Session Break - View Our Virtual Exhibit Hall
12:25 pm Breakout Session

Join your colleagues and fellow delegates for a focused, informal discussion moderated by a member of our speaking faculty.  A small group format allows participants to meet potential collaborators, share examples from their own work and discuss ideas with peers.

BREAKOUT SESSION: Implementation of AI and Machine Learning in Oligonucleotide Design

Anastasia Khvorova, PhD, Professor, RNA Therapeutic Institute, University of Massachusetts Medical School
  • siRNA prediction algorithms opening high-quality datasets​
  • Infrastructure for aggregation of differential datasets and databases
  • Potential for consortium effort

OPTIMIZING DESIGN, DELIVERY AND PERFORMANCE

12:40 pm KEYNOTE PRESENTATION:

Living in the World of RNA Therapeutics Using the GalNAc Conjugates: What Is New?

Mano Manoharan, PhD, Distinguished Scientist & Sr VP Innovation Chem, Innovation Chemistry, Alnylam Pharmaceuticals

GIVLAARI® (2019), OXLUMO® (2020) and LEQVIO®* (2020) are recently approved GalNAc conjugated RNAi Therapeutics. This presentation will point out the molecular basis of their success, and will further illustrate other evolving therapies like Vutrisiran, ALN-AGT and others along with our improvements based on a rational design of siRNAs using Chemical modifications.

Matthew Stone, Biologics Workflow Specialist, SCIEX

Join SCIEX analytical technology experts Matthew Stone and Mukesh Malik during an interactive Q&A session to discuss analytical development and optimization of capillary electrophoresis and liquid chromatography-mass spectrometry based methods for protein characterization and quantification. Exciting topics covered include mAbs and mAb variants, cell and gene therapy, vaccines and more!

1:20 pm

siRNA Chemical Engineering for Extrahepatic Delivery

Anastasia Khvorova, PhD, Professor, RNA Therapeutic Institute, University of Massachusetts Medical School

RNAi enables simple and specific modulation of gene expression when the chemical architecture supporting efficient in vivo delivery is defined. Using huntingtin – the causative gene in Huntington disease – as a model, we demonstrate that chemically engineered siRNAs induce potent protein silencing (> 99%) in all brain regions tested one month post injection. Further chemical optimization enables broad distribution and silencing in large-brain animal models.

1:40 pm

MicroRNA Therapeutics: Targeting the Pathways of Human Disease

Ekkehard Leberer, PhD, Senior Life Sciences Consultant, ELBIOCON; Scientific Managing Director, COMPACT Consortium

MicroRNAs are short non-coding RNAs that regulate biochemical pathways by RNA interference (RNAi). Dysregulation of microRNAs is associated with many diseases. MicroRNA-21 has been implicated with fibrotic diseases and cancer. The presentation shows the development of an anti-fibrotic antisense oligonucleotide (anti-miR-21) for the treatment of a genetic fibrotic kidney disease called Alport Syndrome, and summarizes the potential of anti-miR-21 as a drug to treat hepatocellular carcinoma.

Brian Rivera, Senior Product Manager, Product Management and Strategy, Phenomenex

We will give an overview of sample preparation strategies for synthetic oligonucleotides, including how to adjust experimental design depending on the oligo and sample matrix. We will we go in depth into the parameters to adjust to ensure an effective sample prep and cleanup is implemented and approaches for other challenging oligos which are unique in that they do not have the negatively charged backbone associated with other nucleic acid chemistries.

2:20 pm

A Novel, RNA-Based Anti-Viral Approach to Limit BK Virus Propagation in Immunocompromised Patients


Bianca Matthee, Chief Operating Officer, Hybridize Therapeutics

Polyoma BK virus (BKV) is a highly prevalent latent renal virus that can cause major clinical
issues for immunocompromised patients, which include patients undergoing hematopoietic
stem cell transplantation or kidney transplantation. Although the clinical manifestations may
present slightly differently, both populations are at risk of BKV-associated nephropathy and
graft loss, as well as immediate and severe symptoms such as hemorrhagic cystitis and/or
renal dysfunction. There are currently no treatments for combating BK virus. As such, novel
treatment strategies to limit BKV reactivation are vital. Hybridize has developed an
innovative RNA-based strategy to combat BKV-mediated disease and in this presentation
we will show our approach in abrogating viral DNA replication as well as capsid protein
formation.

2:40 pm

Treating Diseases with Antibody Oligonucleotide Conjugates: Combining the Selectivity of Antibodies with the Specificity of Oligonucleotide Drugs

Arthur A. Levin, PhD, CSO, Avidity Biosciences

Antibody oligonucleotide conjugates (AOCsTM) deliver oligonucleotide therapeutics to multiple cell and tissue types, expanding the therapeutic utility of oligos by combining selective binding of antibodies and specificity of oligonucleotides. Design and engineering AOCs require optimization of the antibody, the oligonucleotide, and the linkers. Taking each of the optimized parts and then optimizing them has enabled us to deliver AOCs to multiple cells and tissues using multiple cell surface-mAb pairs.

3:00 pm

Novel Vaccine Delivery Platforms

Ana Jaklenec, PhD, Research Scientist, Langer Lab, Massachusetts Institute of Technology

Innovative vaccine delivery technologies will be presented including single-injection self-boosting vaccines, 3D printed on-demand micro-needle mRNA vaccines and on patient medical records using invisible dyes.

3:30 pm LIVE PANEL DISCUSSION:

Q&A with Session Speakers

Panel Moderator:
Dmitry Samarsky, PhD, Chief Technology Officer, Sirnaomics
Panelists:
Anastasia Khvorova, PhD, Professor, RNA Therapeutic Institute, University of Massachusetts Medical School
Ekkehard Leberer, PhD, Senior Life Sciences Consultant, ELBIOCON; Scientific Managing Director, COMPACT Consortium
Brian Rivera, Senior Product Manager, Product Management and Strategy, Phenomenex
Bianca Matthee, Chief Operating Officer, Hybridize Therapeutics
Arthur A. Levin, PhD, CSO, Avidity Biosciences
Ana Jaklenec, PhD, Research Scientist, Langer Lab, Massachusetts Institute of Technology
Matthew Stone, Biologics Workflow Specialist, SCIEX
4:00 pm OPT Congress Connects OR Easy Yoga Stretch Break
4:30 pm SC1: Examining the Safety and Toxicity of Nucleic Acid Therapeutics

*Premium REAL TIME VIRTUAL Pricing or separate registration required. See short course page for details.

6:00 pm Close of Oligonucleotide Discovery and Delivery





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