Details

Autor(en) / Beteiligte

• Giangrande, Paloma H.,
• Franciscis, Vittorio de,
• Rossi, John J.,

Titel

RNA therapeutics : the evolving landscape of RNA therapeutics

Ort / Verlag

London, UK : Elsevier,

Erscheinungsjahr

[2022]

Link zum Volltext

• Elsevier Books AutoHoldings

Beschreibungen/Notizen

• Intro -- RNA Therapeutics: The Evolving Landscape of RNA Therapeutics -- Copyright -- Contents -- Contributors -- Section 1 The world of RNA therapeutics: Available RNA tools to modulate cellular processes -- Chapter 1 Targeting chromatin: Transcriptional gene activation (saRNA) -- Discovery and mechanism of action -- Preclinical therapeutic saRNA proof-of-concept studies -- Metabolic and cardiovascular disease -- Genetic disease -- Oncology -- Clinical-stage therapeutic saRNA -- Conclusions -- References -- Chapter 2 Argonaute and TNRC6, partners in RNAi -- Introduction -- Argonaute protein -- Argonaute and RNAi -- Architecture of AGO protein variants -- AGO1-AGO4: Four proteins with distinct and redundant roles -- Nuclear/cytoplasmic distribution of AGO proteins -- Protein binding partners for AGO protein -- TNRC6 protein -- TNRC6 and RNAi -- Architecture of TNRC6 protein variants -- Roles for TNRC6A, TNRC6B, and TNRC6C -- Nuclear/cytoplasmic distribution of TNRC6 proteins -- Protein binding partners for TNRC6 protein -- Tools for analyzing AGO and TNRC6 function -- Nuclear and cytoplasmic purifications -- Available AGO and TNRC6 antibodies -- Protein immunoprecipitation -- RNA sequencing of AGO-bound RNA -- Conclusion -- References -- Chapter 3 Targeted RNA therapeutics for treatment of cancer and immunomodulation -- Lipophilic oligonucleotide conjugates -- Oligonucleotides conjugated with receptor ligands -- Antibody-oligonucleotide conjugates as a delivery strategy -- DNA/RNA aptamers for targeted delivery of oligonucleotide therapeutics -- Oligonucleotide immunotherapeutics targeted to endosomal TLR9 -- Conclusion and perspectives -- Acknowledgments -- References -- Chapter 4 Extrahepatic delivery of RNA to immune cells -- Introduction -- RNA-bio-conjugates for therapeutic and immune cell intervention.
• Antibody and antibody fragments-siRNA conjugates -- Protein-siRNA conjugate -- CpG oligonucleotides-siRNA conjugate -- Aptamer-siRNA conjugates -- Aptamer-TGS siRNA conjugates -- Delivery of miRs and anti-miRs to immune cells -- Supermolecular nanocarriers that manage to deliver RNA to leukocytes for immune cell manipulation -- Polymer-based nanoparticles -- Untargeted polymer-based nanoparticles that deliver RNA to immune cells -- Targeted polymer-based nanoparticles that manage to deliver RNA to immune cells -- Lipid-based nanoparticles -- Targeted liposomes for delivery of RNA to immune cells -- Lipid nanoparticles -- Lipid nanoparticles that deliver RNA to immune cells without targeting ligand -- Targeted lipid nanoparticles that deliver RNA to immune cells by specific targeting ligands -- Discussion -- Acknowledgments -- References -- Section 2 Learning from history -- Chapter 5 Aptamer-based protein inhibitors -- Aptamers as a novel type of protein inhibitors -- Current aptamer-based protein inhibitors for therapeutic application -- Aptamers targeting circulating proteins -- Challenges and advances for aptamer development targeting circulating proteins -- Aptamers targeting cell surface proteins -- Aptamers targeting intracellular proteins -- Aptamers targeting infectious pathogens -- Recent advances and future directions of aptamer-based protein inhibitors -- Improving the SELEX process to isolate aptamer with enhanced binding properties -- Accelerate the SELEX process -- Improving aptamer delivery -- Multivalent aptamer -- Reversible aptamer by antidotes -- Conclusion -- References -- Chapter 6 Lessons learned from developing an oligonucleotide drug for a rare disease -- Introduction -- Duchenne muscular dystrophy is caused by mutations that disrupt the open reading frame.
• Becker muscular dystrophy and revertant fibers: The concept of exon skipping -- Preclinical studies to select a compound for trials -- Scarce cell cultures from rare patients -- Preclinical screening of candidate AOs -- Chemistry, which chemistry? -- Planning a clinical trial for a pediatric rare disease -- Being "trial ready"-registries -- How to measure if a drug works: Clinical and biochemical outcome measures -- Involving regulators early -- Results -- Toxicity -- Approval -- Conclusions -- Collaboration among stakeholders and patients as participants, not subjects -- Future -- Acknowledgments -- Conflict of interest -- References -- Section 3 Delivery -- Chapter 7 Nucleoside modifications of in vitro transcribed mRNA to reduce immunogenicity and improve translation of prophy ... -- Introduction -- Nucleic acids and innate immunity -- Discrimination between endogenous and exogenous RNA -- Origins of the immunogenicity of in vitro transcribed RNA -- Strategies to decrease RNA immunogenicity and improve the translation of in vitro transcribed mRNA sequences -- Capping of the 5′ triphosphate end to decrease immunogenicity and improve translation of in vitro transcribed mRNA -- Nucleoside modifications to abrogate immunogenicity and improve translation of in vitro transcribed mRNA -- Elimination, or prevention, of dsRNA contaminants formed during in vitro transcription -- Conclusion and future perspective -- References -- Chapter 8 SOMAmer reagents and the SomaScan platform: Chemically modified aptamers and their applications in therapeutics, ... -- Introduction -- The advent of SOMAmer reagent technology -- Enhancing chemical diversity -- Enhancing specificity -- Crystal structures -- Post-SELEX modification -- Development of aptamers for therapeutic applications -- The future of aptamer therapeutics.
• Development of an aptamer-based proteomics platform -- Other proteomic technologies -- Specificity and selectivity of the SomaScan platform -- Proteomics discovery on the SomaScan platform -- From comprehensive proteomic profiling to a liquid health check -- Closing remarks -- Acknowledgments -- References -- Section 4 From bench to bedside -- Chapter 9 CMC and regulatory aspects of oligonucleotide therapeutics☆ -- Introduction -- Major classes of RNA therapeutics -- Approved oligonucleotide therapeutics to date -- Most common modifications in therapeutic ONs -- Modification of the internucleotide linkage -- Conjugation strategies -- Modifications of the sugar -- Modification of the nucleobases -- Identification and control of impurities -- Impurity classification -- Conclusions -- Acknowledgments -- References -- Further reading -- Chapter 10 CMC: Regulatory landscape -- Introduction -- High-level view of the CMC process -- Regulatory aspects of the CMC process -- IND module 3-Quality: Content -- Drug substance -- 3.2.S.2 Manufacture -- 3.2.S.2.3 Control of materials -- 3.2.S.2.4 Control of critical steps and intermediates -- 3.2.S.2.5 Manufacturing process validation -- Manufacturing process development -- 3.2.S.3 Characterization -- Identity -- 3.2.S.3.2 Impurities -- Impurity types in oligonucleotide drug substances -- 3.2.S.4 Control of the drug substance -- 3.2.S.4.1 Specifications -- 3.2.S.4.2 Analytical procedures -- 3.2.S.4.3 Validation of analytical procedures -- 3.2.S.4.4 Batch analysis -- 3.2.S.4.5 Justification of specification -- 3.2.S.5 Reference standard materials -- 3.2.S.6 Container closure system -- 3.2.S.7 Stability -- Drug product -- 3.2.P.2 Pharmaceutical development -- 3.2.P.2.2.1 Formulation development -- 3.2.P.2.2.3 Physicochemical properties -- 3.2.P.2.3 Manufacturing process development.
• 3.2.P.2.6 Compatibility-Including sterilization -- 3.2.P.3 Manufacture -- 3.2.P.3.3 Description of manufacturing process and process controls -- 3.2.P.3.5 Process validation and evaluation -- 3.2.P.4 Excipient -- 3.2.P.4.6 Novel excipients -- 3.2.P.5 Control of drug product -- 3.2.P.6 Reference standards -- 3.2.P.8 Stability -- Placebo -- Conclusion: Some take-home messages -- Informal FDA guidance regulator -- European guideline -- References -- Chapter 11 CMC and manufacturing -- Definitions -- Introduction -- Quality principles -- Project life cycle prior to entering the regulated pathway -- From initiation to lead identification -- Entry into the translational research pathway -- Manufacturing process development -- General principles -- Drug substance critical quality attributes -- Chemical entities -- Biotechnological/biological products -- Linking material attributes and process parameters to drug substance CQAs -- Drug substance quality link to drug product -- Control strategy -- Approaches to developing a control strategy -- Consideration in developing a control strategy -- In-process testing -- Starting materials, material needs, and scale-up -- API starting materials -- Understanding project material needs -- Process scale-up -- Chemistry, manufacturing and controls for phase I -- CMC submission section requirements-Introduction -- CMC submission section requirements-Drug substance -- CMC submission section requirements-Drug product -- Lifecycle management -- References -- Section 5 From bench to bedside -- Chapter 12 RNA delivery for cancer gene therapy -- Introduction -- The RNA delivery strategies -- Viral delivery -- Bacterial delivery -- Nanocarrier-based delivery -- Nanoparticles (NPs) and nanostructured materials (NSMs) -- Organic nanocarriers -- Lipid-based nanocarriers -- Polymeric nanocarriers -- Cyclodextrins -- iExosomes.
• Inorganic nanocarriers.
• Provides a comprehensive overview of RNA therapeutic modalities, from bench-to-bedside, with an emphasis on the increasingly impactful areas of gene therapy, oligonucleotide therapeutics, gene editing and delivery. International leaders in the field examine RNA-based therapeutics tools that have been developed to-date to modulate cellular processes such as transcription, translation and protein function. Approved RNA-based therapies and lessons learned from failed therapies are discussed in-depth, as are evolving advances in RNA biochemical analysis, and similar advances that are enabling clinical application of RNA-based therapies. Later sections discuss delivery technologies, remaining hurdles in research and translation, the therapy development process from the lab to the clinic, and novel RNA-based therapies currently in development.
• Description based on print version record.