2017 Archived Content

Emerging Oligonucleotide Therapeutics

Advances in genomics, gene editing, oligonucleotide synthesis, delivery and manufacturing, and an increase in collaborations and licensing opportunities have all contributed to a resurgence in the development of DNA and RNA-based drugs. Although only a handful of oligonucleotide therapeutics are currently approved, more than 125 of them are in various stages of development. Cambridge Healthtech Institute’s Inaugural conference on Emerging Oligonucleotide Therapeutics tracks both the scientific and clinical progress being made in developing new molecular entities, improving synthesis and delivery technologies and extending stability and safety profiles for oligonucleotide-based therapies. It brings together chemists, biologists, pharmacologists and other experts in drug development to share their knowledge and experiences, and to explore areas for active networking and collaborating for bringing to market these novel drug entities.

Final Agenda


• September 25 Symposium: Targeting HBV

• September 26-27 Conference: CRISPR for Disease Modeling and Target Discovery

• September 27-28 Conference: Emerging Oligonucleotide Therapeutics

• September 28-29 Symposium: Tackling Rare Diseases

Wednesday, September 27

11:50 am Conference Registration Open

12:35 pm Plenary Keynote Program

(click here for details)

2:00 Refreshment Break in the Exhibit Hall with Poster Viewing

Development of New Oligonucleotide Platforms and Chemistries

2:45 Welcome Remarks

Tanuja Koppal, Ph.D., Conference Director, Cambridge Healthtech Institute

2:50 Chairperson’s Opening Remarks

Bruce Given, M.D., COO, Arrowhead Pharmaceuticals

2:55 Chemistry Developments and Therapeutic Applications of GalNAc-siRNA Conjugates

Ivan_ZlatevIvan Zlatev, Ph.D., Senior Scientist, Research, Alnylam Pharmaceuticals

3:25 RNAi Based Human Therapy for Chronic Hepatitis B Infection

Amy Lee, Ph.D., Senior Director, In Vivo Pharmacology and Macro-Molecular Discovery, Arbutus Biopharma Corp.

ARB-1467 and ARB-1740 are lipid nanoparticle-delivered RNAi therapeutics currently in Phase II MAD clinical studies. These agents are designed to inhibit viral replication and lower all viral antigens. Reducing HBV proteins, particularly HBsAg, is expected to abrogate viral suppression of immune function and facilitate reinvigoration of the host response/defense. Clinical results to date are promising, with multi-dosing resulting in stepwise, additive reduction in serum HBsAg.

3:55 Late Breaking Presentation 

4:25 Refreshment Break in the Exhibit Hall with Poster Viewing

5:00 Antisense Oligonucleotides: Treating Neurological Disorders at the Level of RNA

Sarah_DeVosSarah L. DeVos, Ph.D., Postdoctoral Fellow, Laboratory of Dr. Bradley T Hyman, Massachusetts General Hospital

Adequate therapies are lacking for neurological disorders, including Alzheimer’s. Antisense oligonucleotides (ASOs) that directly target RNA of disease-associated genes may be therapeutically beneficial. Tau ASOs, for example, have rescued multiple mouse models and show target engagement in non-human primates. These and other data are moving neuro-focused ASOs from “bench to bedside”, with one FDA approved ASO and several others in human clinical trials for neurodegeneration.

5:30 Oligonucleotides with Charge-Neutralizing Branched Groups on the Backbones That Enhance Cellular Uptake

David_TabatadzeDavid R. Tabatadze, Ph.D., President and CEO, ZATA Pharmaceuticals

Novel phosphoramidite monomers enabling the incorporation of charge-neutralizing branched groups (CNBGs) on internucleoside phosphates of oligonucleotides during the automated synthesis have been developed. BCNSs terminated with amino groups form ion pairs with neighboring phosphate groups. Such oligonucleotides possess good solubility and hybridization properties, are not involved in non-standard intramolecular aggregation, have low cytotoxicity, adequate chemical stability, improved serum stability, and display significantly enhanced cellular uptake.

6:00 Characterization of Novel Conjugated RNAi drugs

Bruno GodinhoBruno M.D.C. Godinho, PhD., Milton-Safenowitz Post-Doctoral Fellow, Laboratory of Dr. Anastasia Khvorova, RNA Therapeutics Institute, University of Massachusetts Medical School

Clear understanding of the PK/PD behavior is essential for characterizing the performance of RNAi-based drug candidates in vivo. As novel conjugated oligonucleotides emerge in the field, simple and reproducible methodologies are required to facilitate and accelerate systematic assessment of these compounds. Strategies for chemical stabilization oligonucleotide constructs, a platform for evaluation of PK and biodistribution, and a high throughput method for assessment of efficacy are three key pillars for characterization of RNAi-based compounds.

6:30 Close of Day

6:30 Dinner Short Course Registration

Click here for details on short courses offered.

Thursday, September 28

7:30 am Registration Open

8:00 Interactive Breakout Discussion Groups with Continental Breakfast

Grab a cup of coffee and join a breakout discussion group. These are informal, moderated discussions with brainstorming and interactive problem solving, allowing participants from diverse backgrounds to exchange ideas and experiences and develop future collaborations around a focused topic. Details on the topics and moderators are below. Please click here for full details on all breakouts.

Considerations for Therapeutic Translation of CRISPR/Cas9


Eric B. Kmiec, Ph.D., Director, Gene Editing Institute and Senior Research Scientist, Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System


  • Potential human applications of genome editing to somatic cells
  • Scientific and technical considerations for design and application of genome editing strategies
  • Ethical and regulatory issues associated with somatic cell genome editing
  • Development of reproducible and robust strategies that can enable precise point mutation repair or gene insertion
  • Types of experimental variabilities with the use of different cell lines; established cell lines, iPSCs and primary cells in general


Designing and Delivering Better Oligonucleotide Drugs

Moderators: Dan Peer, Ph.D., Director, Laboratory of Precision NanoMedicine, Tel Aviv University 

Bruce Given, M.D., COO, Arrowhead Pharmaceuticals

  • Is delivery the only challenge that will change the fate of oligonucleotide therapies?
  • What are the challenges and opportunities in modulating the immune system with oligonucleotide drugs?
  • Can we design improved and local oligo therapeutics? In what indications? Examples from siRNA, modified mRNA and CRISPR /Cas will be considered. 


Exploring CRISPR and Other Innovative Drug Modalities

9:00 Chairperson’s Remarks

Thomas D. Madden, Ph.D., President and CEO, Acuitas Therapeutics

9:05 Therapeutic Protein Expression in vivo Using Messenger RNA-Lipid Nanoparticles

Thomas_MaddenThomas D. Madden, Ph.D., President and CEO, Acuitas Therapeutics

Messenger RNA (mRNA) is an important new therapeutic modality. However mRNA is labile and requires a delivery system to access cells. New generations of lipid nanoparticle systems (LNP) allow efficient delivery and expression of mRNA via different routes of administration. Key parameters impacting potency and safety will be discussed. In addition preclinical results illustrating the application of mRNA-LNP therapeutics in a several clinical areas will be presented.

9:35 Using Single-Stranded Donor DNA for Homology Directed Repair Catalyzed by CRISPR/Cas9 Activity

Eric_KmiecEric. B. Kmiec, Ph.D., Director, Gene Editing Institute and Senior Research Scientist, Center for Translational Cancer Research, Helen F. Graham Cancer Center & Research Institute, Christiana Care Health System

This talk will focus on utilizing the information gathered from studies on the mechanism of action and regulatory circuitry surrounding gene editing using single-stranded oligonucleotides in combination with CRISPR/Cas9. We will examine how genetic lesions often arise during the process of homology directed repair and point mutation resolution. Examples will be provided outlining the strategy for carrying out genetic surgery more precisely and how they may enable productive outcomes in the clinic.

10:05 Efficacy of U1 Adaptor Gene Silencing of the Undruggable KRAS and MYC Oncogenes in Xenograft Mice

Samuel Gunderson, Ph.D., President and Co-Founder, SilaGene Inc.

U1 Adaptors oligonucleotides (U1AOs) interfere with polyadenylation of gene-specific mRNA, causing their selective destruction inside the nucleus. U1AOs can accept extensive covalent modifications for nuclease resistance and conjugation to tumor-targeting peptides without loss of silencing activity, offering important advantages as therapeutic agents. Systemically delivered U1AO-peptide conjugates targeting KRAS and MYC lead to tumor shrinkage in xenograft mice harboring pancreatic cancer with no apparent toxicity.

10:35 Coffee Break in the Exhibit Hall with Poster Viewing and Poster Competition Winner Announced

Oligonucleotides for Cancer Immunotherapy

11:20 RNAi-Mediated β-Catenin Inhibition Promotes T Cell Infiltration and Potentiates Immune Checkpoint Blockade

Shanthi Ganesh, Ph.D., Associate Director, Pre Clinical Oncology, Dicerna Pharmaceuticals, Inc.

Recent research implicates Wnt/β-catenin signaling as a mechanism of resistance to cancer immunotherapy. DCR-BCAT is an RNAi-based experimental drug targeting β-catenin, formulated in a tumor-selective nanoparticle. In preclinical models, systemic administration of DCR-BCAT induced rapid increases in tumor T cells and dramatically improved responses to immunotherapy agents. In this presentation, we explore the mechanism of synergistic efficacy and suggest clinical evaluation of this first-in-class RNAi agent.

11:50 SB 11285, a Novel STING Agonist for ImmunoTherapy of Cancer

Kris_IyerR.P. (Kris) Iyer, Ph.D., Co-Founder & CSO, Spring Bank Pharmaceuticals

Immunotherapy has emerged as a transformative approach for the treatment of cancer. Evidence suggests that the activation of Stimulator of Interferon Genes (STING) pathway in tumor cells and/or immune cells induce type I Interferon production leading to apoptosis of tumor cells, as well as, induction of adaptive immune response thereby providing a powerful anti-cancer strategy. Herein, we describe the discovery and preclinical studies of SB 11285, a novel STING agonist for application in immuno-oncology.

12:20 Enjoy Lunch on Your Own

1:50 Refreshment Break in the Exhibit Hall with Poster Viewing

Tackling Challenges with Delivery

2:35 Chairperson’s Remarks

Dan Peer, Ph.D., Director, Laboratory of Precision NanoMedicine, Tel Aviv University

2:40 Moving from Intravenous to Subcutaneous Delivery in RNAi – Why and How

Bruce GivenBruce D. Given, M.D., COO, Arrowhead Pharmaceuticals

RNA interference (RNAi) occurs in the cytoplasm. RNAi triggers are routed on cell entry through endosomes, which are well equipped to metabolize RNA and to initiate host immune responses. Legacy delivery systems require mechanisms for endosomal escape and intravenous dosing. Advances in RNAi trigger chemistry and targeting allow effective knockdown without requiring active endosomal escape, without toll receptor activation and allowing subcutaneous delivery.

3:10 From Local to Systemic: Delivering Novel siRNA Therapeutics for Multiple Clinical Indications

Patrick Y. Lu, Ph.D., President & CEO, Sirnaomics, Inc.

Sirnaomics is trying to use its proprietary and optimized polypeptide-based delivery technology, to develop the novel anti-fibrotic RNAi therapeutics targeting both TGFβ1 and Cox-2 simultaneously. The initial indication is to treat skin hypertrophic scar and then extend it to liver fibrosis, such as Primary Sclerosing Cholangitis, and liver cancer, such as Cholangicarcinoma, as well as other fibrotic conditions. With INDs approved by both U.S. FDA and China FDA, we have started clinical trials in both countries. I will discuss the unique advantage of this polypeptide nanoparticle technology for efficient siRNA delivery, its pharmaceutical properties for manufacturing and its preclinical safety profile.

3:40 Session Break

3:55 A Multi-Dimensional RNA-Based Approach to Treat Genetic Disorders

John Androsavich, Ph.D., Senior Scientist, Translate Bio

Many genetic diseases can be treated by restoring defective gene expression. We can activate gene expression by three distinct technology platforms: 1) Targeting repressive cis-acting long noncoding RNA, 2) Enhancing stability of mRNA transcript, or 3) Supplementing in vitro transcribed mRNA. With these three different platforms, we can achieve specific gene upregulation and tailor to desired therapeutic profiles. Recent progress in the discovery and preclinical development of all three platforms will be presented.

4:25 Targeted Platform for RNA Therapeutics

Dan_PeerDan Peer, Ph.D., Director, Laboratory of Precision NanoMedicine, Tel Aviv University

The translation of RNA from an effective genomic tool into a novel therapeutic modality has been hindered by the difficulty to deliver RNA molecules into specific target tissues by systemic administration, especially to leukocytes. Here, I will describe some of the challenges and opportunities in modulating leukocytes response using RNA molecules and discuss adverse effects such as immuno-toxicity. In addition, I will detail the challenges of targeting lipid-based nanoparticles directly into specific cells.

4:55 Close of Conference