RNA Therapeutics: The Evolving Landscape of RNA Therapeutics (Paperback)

Section I: The world of RNA Therapeutics 1. Targeting DNA (chromatin): Transcriptional gene silencing, Transcriptional gene activation, CRISPR/Cas9 2. Targeting RNA (mRNA, lncRNAs): Antisense, splice switching oligos, siRNAs (including dsRNAs), miRNAs 3. Targeting proteins (functional protein ligands): Aptamers, TLR agonists/antagonists (CpG oligos), mRNA

Section II: Learning from history Overview 4. RNA therapies: Early days to present 5. RNAseH-mediate therapies 6. Protein inhibition with aptamers (Pegaptanib L Gold, Regado’s REG1, REG2, REG3 and antidote technology), what have we learned 7. Antisense: exon skipping (eteplirsen), exon inclusion (nusinersen), lessons learned, first global approval (inotersen- TTR), implications 8. RNA interference: Patisiran, next wave of RNAi drugs 9. MRX34 Phase I clinical study

Section III: RNA Chemistry Overview 10. ASO modifications: PNA (IONIS) 11. Modifications for mRNA therapeutics 12. Chemically-modified nucleic acids: stability and permeability 13. Expanded genomics 14. LNA and Gapmers 15. A guide to CRISPR

Section IV: Delivery Overview 16. Viral delivery 17. Nanoparticles and nanostructures 18. Ligand-mediated delivery: Targeted delivery: Aptamer 19. Pharmacodynamics, pharmacokinetic, bioavailability, biodistribution, route of administration 20. Extra hepatic delivery: Challenges and novel approaches

Section V: From Bench to Bedside Overview 21. Path from Discovery to filing IND 22. Regulatory landscape 23. CMC and manufacturing 24. Toxicology and Safety considerations

Section VII: The future of RNA therapies ? where are we headed? 25. What is the niche for RNA based therapies vs. small molecule drugs and ERT (protein/antibody drugs) 26. Longer RNAs: mRNA therapies 27. Novel mechanisms: saRNAs 28. CRISPR/Cas: discuss ex vivo and in vivo applications 29. Combinatorial RNA therapies: AsiCs and CpG conjugates 30. Beyond the liver