RNA Therapeutics

Dr. Paloma Giangrande is the VP of Biology at Wave Life Sciences, Cambridge, MA and Adjunct Associate Professor of Internal Medicine at the University of Iowa, Iowa City, IA. Her career has been dedicated to the investigation and development of RNA-based therapeutic approaches (including RNA aptamers, siRNAs, and mRNA) for cancer, cardiovascular disease, rare diseases, and critical illness. As a consequence, she has developed a deep understanding of these technologies, diseases, and associated disease mechanisms. She is also an internationally recognized expert in oligonucleotide therapeutics and delivery. Towards this end, she was the first to demonstrate that RNA ligands (aptamers) can be used to deliver therapeutic siRNAs to target cells. Her 60+ publications and 9+ patents are a testament to this body of work and her commitment to the development of novel RNA-based therapies for many diseases. Dr. Vittorio de Franciscis is Senior Collaborator at the CNR Institute of Genetic and Biomedical Research (IRGB) in Milan Italy. For more than ten years, the interest of the research has focused on translating the understanding of the molecular basis of neoplastic transformation in the design of selective therapies based on the use of therapeutic RNAs (aptamers, siRNAs, miRNAs). In his laboratory, they demonstrated the possibility of generating aptamers that bind to high affinity and inhibit transmembrane receptors involved in cancer progression (including, EGFR, AXL, PDGFR, IR, Eph).?For the selection of aptamers they have developed a variant of the SELEX technology that makes use of living cells as a complex target.?They have recently shown that such RNA aptamers against RTK can be used as targeting moieties for the selective delivery of therapeutic miRNAs and anti-miRs, against tumor cells and tissues.

SECTION 1 The world of RNA therapeutics: Available RNA tools to modulate cellular processes 1. Targeting chromatin: Transcriptional gene activation (saRNA) 2. Argonaute and TNRC6, partners in RNAi 3. Targeted RNA therapeutics for treatment of cancer and immunomodulation 4. Extrahepatic delivery of RNA to immune cells

SECTION 2 Learning from history 5. Aptamer-based protein inhibitors 6. Lessons learned from developing an oligonucleotide drug for a rare disease

SECTION 3 Delivery 7. Nucleoside modifications of in vitro transcribed mRNA to reduce immunogenicity and improve translation of prophylactic and therapeutic antigens 8. SOMAmer reagents and the SomaScan platform: Chemically modified aptamers and their applications in therapeutics, diagnostics, and proteomics

SECTION 4 From bench to bedside 9. CMC and regulatory aspects of oligonucleotide therapeutics 10. CMC: Regulatory landscape 11. CMC and manufacturing

SECTION 5 From bench to bedside 12. RNA delivery for cancer gene therapy 13. Combinatorial RNA therapies in cancer immunotherapy: Challenges and directions