This volume presents a comprehensive collection of detailed state-of-the-art protocols for gapmer-mediated RNA knockdown from leaders in the field. Chapters detail a historical and contemporary perspective of RNase H-inducing antisense oligonucleotides called gapmers and gapmer-mediated RNA knockdown for basic research and therapies. Written in the highly successful Methods in Molecular Biology series format, chapters include introductions to their respective topics, lists of the necessary materials and reagents, step-by-step, readily reproducible laboratory protocols, and tips on troubleshooting and avoiding known pitfalls. Authoritative and cutting-edge, Gapmers: Methods and Protocols aims to provide diverse applications of gapmers along with protocols that will assist readers in moving the frontier.

Extensively revised and updated, Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition reflects the logarithmic progress made in the past four years of oligonucleotide-based therapies, and, in particular, antisense therapeutics and research. Interpreting lessons learned from the clinical trials of first generation drugs, the book evaluates the technology as a whole and offers new directions and avenues of research and development. Divided into five parts, the book begins with a thorough introduction to the mechanism of antisense drug action including the RNase H mechanism, small RNA silencing pathways, and the potential therapeutics of splice switching oligonucleotides. Leading researchers demonstrate the basics of oligonucleotide therapeutics in part two by delineating medicinal chemistry, pharmacokinetics, and delivery routes such as liposomal formulations for nucleic acid delivery. Part three details hybridization based drugs and considers the dramatic advances represented by 2’ methoxyethyl chimeric antisense inhibitors and duplex RNA drugs. Other chemical classes of drugs and mechanisms of action are described in part four with further discussions on improving the second generation antisense drugs. The final part delves deeply into therapeutic applications. Contributing authors examine the potential of antisense drugs for the alleviation of cardiovascular diseases, metabolic diseases, inflammatory diseases, cancer, neurological disorders, and immune modulation. Presenting a highly detailed, lucid discussion of the remarkable advances in the field, Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition provides the platform for researchers to continue to aggressively pursue the great opportunity represented by this exciting technology.

A comprehensive review of contemporary antisense oligonucleotides drugs and therapeutic principles, methods, applications, and research Oligonucleotide-based drugs, in particular antisense oligonucleotides, are part of a growing number of pharmaceutical and biotech programs progressing to treat a wide range of indications including cancer, cardiovascular, neurodegenerative, neuromuscular, and respiratory diseases, as well as other severe and rare diseases. Reviewing fundamentals and offering guidelines for drug discovery and development, this book is a practical guide covering all key aspects of this increasingly popular area of pharmacology and biotech and pharma research, from the basic science behind antisense oligonucleotides chemistry, toxicology, manufacturing, to safety assessments, the design of therapeutic protocols, to clinical experience. Antisense oligonucleotides are single strands of DNA or RNA that are complementary to a chosen sequence. While the idea of antisense oligonucleotides to target single genes dates back to the 1970's, most advances have taken place in recent years. The increasing number of antisense oligonucleotide programs in clinical development is a testament to the progress and understanding of pharmacologic, pharmacokinetic, and toxicologic properties as well as improvement in the delivery of oligonucleotides. This valuable book reviews the fundamentals of oligonucleotides, with a focus on antisense oligonucleotide drugs, and reports on the latest research underway worldwide. • Helps readers understand antisense molecules and their targets, biochemistry, and toxicity mechanisms, roles in disease, and applications for safety and therapeutics • Examines the principles, practices, and tools for scientists in both pre-clinical and clinical settings and how to apply them to antisense oligonucleotides • Provides guidelines for scientists in drug design and discovery to help improve efficiency, assessment, and the success of drug candidates • Includes interdisciplinary perspectives, from academia, industry, regulatory and from the fields of pharmacology, toxicology, biology, and medicinal chemistry Oligonucleotide-Based Drugs and Therapeutics belongs on the reference shelves of chemists, pharmaceutical scientists, chemical biologists, toxicologists and other scientists working in the pharmaceutical and biotechnology industries. It will also be a valuable resource for regulatory specialists and safety assessment professionals and an important reference for academic researchers and post-graduates interested in therapeutics, antisense therapy, and oligonucleotides.

The sequencing of the human genome and subsequent elucidation of the molecular pathways that are important in the pathology of disease have provided unprecedented opportunities for the development of new therapeutics. Nucleic acid-based drugs have emerged in recent years to yield extremely promising candidates for drug therapy to a wide range of diseases. Advances in Nucleic Acid Therapeutics is a comprehensive review of the latest advances in the field, covering the background of the development of nucleic acids for therapeutic purposes to the array of drug development approaches currently being pursued using antisense, RNAi, aptamer, immune modulatory and other synthetic oligonucleotides. Nucleic acid therapeutics is a field that has been continually innovating to meet the challenges of drug discovery and development; bringing contributions together from leaders at the forefront of progress, this book depicts the many approaches currently being pursued in both academia and industry. A go-to volume for medicinal chemists, Advances in Nucleic Acid Therapeutics provides a broad overview of techniques of contemporary interest in drug discovery.

This book provides a compelling overall update on current status of RNA interference

Extensively revised and updated, Antisense Drug Technology: Principles, Strategies, and Applications, Second Edition reflects the logarithmic progress made in the past four years of oligonucleotide-based therapies, and, in particular, antisense therapeutics and research. Interpreting lessons learned from the clinical trials of first generati

This volume presents techniques needed for the study of long non-coding RNAs (lncRNAs) in cancer from their identification to functional characterization. Chapters guide readers through identification of lncRNA expression signatures in cancer tissue or liquid biopsies by RNAseq, single Cell RNAseq, Phospho RNAseq or Nanopore Sequencing techniques; validation of lncRNA signatures by Real time PCR, digital PCR or in situ hybridization; and functional analysis by siRNA or CRISPR based methods for lncRNA silencing or overexpression. Lipid based nanoparticles for delivery of siRNAs in vivo, lncRNA-protein interactions, viral lncRNAs and circRNAs are also treated in this volume. Written in the format of the highly successful Methods in Molecular Biology series, each chapter includes an introduction to the topic, lists necessary materials and reagents, includes tips on troubleshooting and known pitfalls, and step-by-step, readily reproducible protocols. Authoritative and practical, Long Non-Coding RNAs in Cancer aims to provide a collection of laboratory protocols, bioinformatic pipelines, and review chapters to further research in this vital field.