LEADER 05711nam 2200709Ia 450 001 9910815366903321 005 20200520144314.0 010 $a1-118-61073-3 010 $a1-118-61074-1 010 $a1-299-46528-5 010 $a1-118-61075-X 035 $a(CKB)2550000001019426 035 $a(EBL)1166922 035 $a(OCoLC)850209522 035 $a(SSID)ssj0000855714 035 $a(PQKBManifestationID)11440512 035 $a(PQKBTitleCode)TC0000855714 035 $a(PQKBWorkID)10804846 035 $a(PQKB)10701429 035 $a(MiAaPQ)EBC1166922 035 $a(DLC) 2013014058 035 $a(Au-PeEL)EBL1166922 035 $a(CaPaEBR)ebr10687823 035 $a(CaONFJC)MIL477778 035 $a(PPN)178710350 035 $a(EXLCZ)992550000001019426 100 $a20130330d2013 uy 0 101 0 $aeng 135 $aur|n|---||||| 181 $ctxt 182 $cc 183 $acr 200 00$aAdvanced delivery and therapeutic applications of RNAi /$fedited by Kun Cheng, Ram I. Mahato 205 $a2nd ed. 210 $aChichester, West Sussex $cJohn Wiley & Sons Inc.$d2013 215 $a1 online resource (535 p.) 300 $aDescription based upon print version of record. 311 $a1-119-97686-3 320 $aIncludes bibliographical references and index. 327 $aAdvanced Delivery and Therapeutic Applications of RNAi; Contents; Preface; Contributors; About the Editors; Part 1: Introduction and Basics of RNAi; 1 Mechanisms and Barriers to RNAi Delivery; 1.1 Introduction; 1.2 Barriers to Systemic RNAi Delivery; 1.3 Rational Design to Improve RNAi Efficacy; 1.4 Chemical Modifications to Enhance siRNA Stability and Reduce Immune Response; 1.5 Cellular Uptake and Intracellular Release of siRNA; 1.6 Combinatorial Targeting for Targeted RNAi Delivery; 1.7 Cell-Specific Aptamer-Functionalized Nanocarriers for RNAi Delivery 327 $a1.8 The Clinical Development and Challenges of siRNAs Therapeutics1.9 Conclusion and Perspectives; References; 2 Analysis of siRNA Delivery Using Various Methodologies; 2.1 Introduction; 2.2 Checkpoints for Analyzing siRNA Delivery; 2.2.1 Circulation Checkpoint; 2.2.2 Organ or Tissue Checkpoint; 2.2.3 Cellular Checkpoint; 2.2.4 RISC Checkpoint; 2.2.5 Target mRNA Knockdown (Indirect Checkpoint); 2.2.6 Protein and Outcome (Indirect Checkpoint); 2.2.7 Safety (Indirect Checkpoint); 2.3 Methods for Analysis of siRNA; 2.3.1 General Considerations; 2.3.2 Hybridization-Based (Non-Imaging) Methods 327 $a2.3.3 Non-Hybridization-Based (Non-Imaging) Methods2.3.4 Imaging-Based (Non-Hybridization) Methods; 2.3.5 Imaging-Based (Hybridization) Methods; 2.4 Case Study for siRNA Delivery Analysis; References; 3 Challenges and Opportunities in Bringing RNAi Technologies from Bench to Bed; 3.1 Introduction; 3.2 RNAi Mediator (siRNA or shRNA); 3.2.1 siRNA; 3.2.2 Vector-derived shRNA; 3.2.3 miRNAs; 3.3 Safety Issues of RNAi Mediators; 3.3.1 Immune Stimulation; 3.3.2 RNAi Overexpression; 3.4 Efficacy of RNAi Mediators; 3.4.1 Therapeutic Response; 3.5 RNAi Mediators in Clinical Trials; 3.6 Conclusion 327 $aReferences4 Nonclinical Safety Assessments and Clinical Pharmacokinetics for Oligonucleotide Therapeutics: A Regulatory Perspective; 4.1 Introduction; 4.2 Unique Properties of Oligonucleotide-based Therapeutics; 4.3 Regulation of Oligonucleotide-Based Therapeutics; 4.3.1 Submission to the FDA; 4.3.2 Review Process for Non-clinical Studies; 4.3.3 Regulatory Issues; 4.3.4 Clinical Pharmacokinetics; 4.4 Conclusion; Disclaimer; Appendix; References; 5 Role of Promoters and MicroRNA Backbone for Efficient Gene Silencing; 5.1 Introduction; 5.2 Promoters for shRNA Expression 327 $a5.2.1 Constitutive Promoters5.2.2 Inducible Promoters; 5.2.3 Site Specific Promoters; 5.3 miRNA-based shRNAs; 5.3.1 miRNA-based shRNA Enhances Gene Silencing; 5.3.2 miRNA-based shRNA Reduces Toxicities; 5.3.3 Application of miRNA-based shRNA for Combination Gene Therapy; 5.4 Concluding Remarks; References; Part 2: RNAi Delivery Strategies; 6 Bioconjugation of siRNA for Site-specific Delivery; 6.1 Introduction; 6.2 Conjugation Strategy; 6.2.1 RNA Chemical Modification; 6.2.2 Site of Conjugation; 6.2.3 Conjugation Chemistry; 6.3 Bioconjugates for Site-specific Delivery 327 $a6.3.1 Antibody-siRNA Bioconjugates 330 $a"Commonly used by researchers to develop technologies for modifying and studying genetic process, RNA interference (RNAi) has many potential uses in medicine, biotechnology, and functional genomics. This book covers all essential aspects involved in the development of RNAi therapeutics, providing detailed guidance on the challenges and opportunities of bringing RNAi technologies from bench to clinic. It explores the design and mechanism of RNAi molecules, delivery strategies, and therapeutic applications in various diseases. Preclinical, regulatory, market, and intellectual aspects of RNAi technologies are also covered"--$cProvided by publisher. 330 $a"All of the essential aspects of developing RNAi therapeutics from bench to clinic presented in a single volume"--$cProvided by publisher. 606 $aRNA$xTherapeutic use 606 $aSmall interfering RNA$xTherapeutic use 615 0$aRNA$xTherapeutic use. 615 0$aSmall interfering RNA$xTherapeutic use. 676 $a572.8/8 686 $aSCI013040$2bisacsh 701 $aCheng$b Kun$0923418 701 $aMahato$b Ram I$0940187 801 0$bMiAaPQ 801 1$bMiAaPQ 801 2$bMiAaPQ 906 $aBOOK 912 $a9910815366903321 996 $aAdvanced delivery and therapeutic applications of RNAi$94001126 997 $aUNINA