Length:136 pages

Date Published:October 2010 

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RNAi Therapeutics: Second-Generation Candidates Build Momentum Report - Table of Contents

Author: Allan B. Haberman, PhD

EXECUTIVE SUMMARY 

CHAPTER 1
INTRODUCTION  
1.1 Development of Other Types of Oligonucleotide Therapeutics has been Leading the way to Developing RNAi Therapeutics 
1.2 Implications of the Development of Antisense and Aptamer Drugs for the Therapeutic RNAi Field 
 

CHAPTER 2
SMALL SILENCING RNAs, AND MECHANISMS OF RNA INTERFERENCE 
2.1 The RNAi Pathway 
microRNAs: Processing and Silencing Pathways  
PIWI-interacting RNAs 
2.2 Transcriptional Gene Silencing by siRNA and miRNA 
Small Silencing RNAs in the Universe of Small Regulatory RNAs 
 

CHAPTER 3
DESIGN OF INTERFERING RNAs 
3.1 RNAi Therapeutics Now in Clinical Development  
3.2 Challenges in Designing Oligonucleotides as Therapeutic RNAi Agents  
3.3 Design of siRNAs to Avoid Innate Immune Activation 
siRNA therapeutics designed to trigger both immunostimulation and specific RNAi 
Getting naked RNAs into the cell in experimental in vitro and in vivo studies of potential RNA therapeutics  
3.4 Alternative Designs of Interfering Oligonucleotides Being Developed by Leading Companies  
Dicerna’s Dicer Substrate Technology 
RXi’s proprietary RNAi compounds  
rxRNAori  
rxRNA solo 
sd-rxRNA 
3.5 Conclusions   

CHAPTER 4 
DEVELOPMENT OF DELIVERY VEHICLES FOR RNAi DRUGS 
4.1 Direct Delivery of siRNA Therapeutics 
Alnylam/Kyowa Hakko Kirin/ Cubist’s ALN-RSV01 
Pfizer/Quark/Silence’s PF-4523655 
RXi’s sd-rxRNA platform for local delivery 
4.2 Alnylam’s Use of Tekmira’s SNALP Technology for System Delivery of siRNA Therapeutics to the Liver  Second-generation SNALP technologies  
4.3 RXi’s siRNA Systemic Delivery Platforms  
4.4 Calando’s Rondel Delivery System 
4.5 Silence Therapeutics’s AtuPLEX and PolyTran Delivery Platforms  

AtuPLEX delivery system 
PolyTran delivery system 
4.6 Delivery Vehicle for siRNA Designed to Cross the Blood-Brain Barrier 
4.7 Conclusions 
 

CHAPTER 5 
LEADING COMPANIES IN THE THERAPEUTIC RNAi FIELD 
5.1 Alnylam Pharmaceuticals 
Alnylam’s strategy 
Alnylam’s collaborations  
Alnylam’s candidate products 
Alnylam’s ventures 
5.2 Tekmira Pharmaceuticals  
5.3 Sirna Therapeutics/Merck 
5.4 RXi Pharmaceuticals 
5.5 Calando Pharmaceuticals 
5.6 Silence Therapeutics 
5.7 Quark Pharmaceuticals 
QPI-1002 
QPI-1007 
Quark’s collaborations   
Quark’s 2010 $10 million financing 
5.8 Dicerna Pharmaceuticals Dicerna’s collaborations 
5.9 Summary table 
5.10 The Role of Big Pharma in the Development of siRNA Therapeutics 
 

CHAPTER 6 
LEADING COMPANIES IN miRNA THERAPEUTICS 
6.1 Regulus Therapeutics 
Regulus’ alliances 
Regulus’ products  
Regulus’ “tool kit” for designing miR-122 antagonists and antagonists to other miRNAs 
miR-21 and fibrosis 
Other miRNA-based discovery/development programs at Regulus 
6.2 Santaris Pharma Santaris’ partners 
Santaris’ pipeline
6.3 miRagen Therapeutics miRagen’s technology platform 
miRagen’s alliances 
miRagen’s pipeline 
6.4 Summary table  
6.5 The Role of Big Pharma in the Development of miRNA Therapeutics 
miRNA diagnostics 

CHAPTER 7
OUTLOOK FOR RNAi THERAPEUTICS 
7.1 Is Therapeutic RNAi Technologically Premature? 
7.2 Why is Big Pharma so Interested in Investing in RNAi and miRNA Therapeutics? 
7.3 Patents, Lawsuits and the Development of the RNAi/miRNA Sector 
7.4 A Scenario for the Development of Drugs in the Therapeutic RNAi/miRNA Sector  
 

CHAPTER 8
EXPERT INTERVIEWS 
8.1. Dalia Cohen, PhD, Chief Scientific Officer, Rosetta Genomics, Philadelphia, PA 
8.2. Roberto Guerciolini, MD, Senior Vice President, Pharmaceutical Developmen, Dicerna Pharmaceuticals, Watertown, MA 
8.3. Arthur M. Krieg, MD, Chief Scientific Officer, Oligonucleotide Therapeutics Unit, Pfizer, Cambridge, MA 
8.4. William S. Marshall, PhD,President and Chief Executive Officer, miRagen Therapeutics, Boulder, CO  
8.5. James D. Thompson, PhD, Vice President, Pharmaceutical Development, Quark Pharmaceuticals, Boulder, CO 
 

REFERENCES  

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