RNA Interference in the Post-Genomic Era: Markets and Technologies

Published by: BCC Research

Published: Feb. 1, 2008

Table of Contents

INTRODUCTION

STUDY GOALS AND OBJECTIVES

REASONS FOR DOING THE STUDY

CONTRIBUTION OF THE STUDY AND FOR WHOM

SCOPE OF REPORT

METHODOLOGY

INFORMATION SOURCES

RELATED BCC REPORTS

ANALYST CREDENTIALS

BCC ONLINE SERVICES

DISCLAIMER

SUMMARY

SUMMARY TABLE GLOBAL VALUE OF RNA INTERFERENCE MARKET BY MARKET SEGMENT, THROUGH 2013 ($ MILLIONS)

SUMMARY FIGURE GLOBAL VALUE OF RNA INTERFERENCE MARKET BY MARKET SEGMENT, 2006-2013 ($ MILLIONS)

OVERVIEW

INTRODUCTION

CONVERGENCE OF POST GENOME TECHNOLOGIES

TABLE 1 POST GENOME ENABLING TOOLS

TABLE 2 NEW PARADIGM OF RNA INTERFERENCE

MARKET POTENTIAL OF RNA INTERFERENCE-BASED

PRODUCTS

GLOBAL RNAI MARKET FORECAST

TABLE 3 GLOBAL VALUE OF RNA INTERFERENCE MARKET BY MARKET SEGMENT, THROUGH 2013 ($ MILLIONS)

GLOBAL RNAI RESEARCH TOOLS MARKET

TABLE 4 GLOBAL VALUE OF RNA INTERFERENCE RESEARCH TOOLS MARKET BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS)

TABLE 5 GLOBAL VALUE OF RNA INTERFERENCE DRUG MARKET, BY CLASS, THROUGH 2013 ($ MILLIONS)

GROWTH DRIVING FORCES IN RNA INTERFERENCE MARKETS

TABLE 6 PRIMARY FORCES DRIVING RNA INTERFERENCE GROWTH

RNA INTERFERENCE: BUILDING ON ANTISENSE TECHNOLOGIES

TABLE 7 KEY ANTISENSE CONTRIBUTIONS TO RNA INTERFERENCE

APPLICATIONS OF RNA INTERFERENCE

RNA INTERFERENCE AS A GENE KNOCKDOWN

TECHNOLOGY

RNA INTERFERENCE AS A BIOMARKER

RNA INTERFERENCE IN THERAPEUTICS

RNA INTERFERENCE IN AGRICULTURE

THE RNA INTERFERENCE INDUSTRY

The RNA Interference Industry (Continued)

RNA INTERFERENCE TECHNOLOGIES

INTRODUCTION

ROLE OF MESSENGER RNA IN PROTEIN PRODUCTION

FIGURE 1 ROLE OF MESSENGER RNA IN PROTEIN PRODUCTION

TABLE 8 BASIC STEPS IN PROTEIN PRODUCTION

RNA INTERFERENCE PROCESS

FIGURE 2 RNA INTERFERENCE PROCESS

GENE SILENCING TECHNOLOGIES

TABLE 9 COMPARISON OF RNA INTERFERENCE AND ANTISENSE OLIGO TECHNOLOGIES

TABLE 10 SHORT INTERFERING, SHORT HAIRPIN, AND MICRO RNA VERSUS OLIGO ANTISENSE TECHNOLOGIES

TABLE 10 (CONTINUED)

SHORT HAIRPIN RNA

MICRO RNA

Introduction

miRNAs and Cancer

miRNA Biogenesis

FIGURE 3 MICRO RNA BIOGENESIS

SIRNAS

RNA INTERFERENCE HISTORY

TABLE 11 RNA INTERFERENCE HISTORY

TABLE 11 (CONTINUED)

RNAI: BUILDING ON AN ANTISENSE TECHNOLOGY PLATFORM

TABLE 12 ANTISENSE TECHNOLOGY PLATFORMS

APPLICATIONS OF RNA INTERFERENCE

TABLE 13 NEAR TERM RNA INTERFERENCE COMMERCIAL APPLICATIONS

SIRNA TECHNOLOGY

SIRNA PRODUCTION TECHNOLOGIES

TABLE 14 COMPARISON OF METHODS FOR PRODUCING SHORT INTERFERING RNA

TABLE 14 (CONTINUED)

Chemical Synthesis

In vitro Transcription

In vitro Transcription Followed by Dicer Digestion (Dicer

Substrate siRNA)

PCR Expression Cassettes

Plasmid or Viral Vector Expression

SHORT INTERFERING RNA LIBRARIES

RNA INTERFERENCE RESEARCH TOOL PRODUCTS

FIGURE 4 RNA INTERFERENCE RESEARCH TOOLS PRODUCTS SIRNA EFFECTORS

TABLE 15 COMPARISON OF SYNTHETIC AND PLASMID SHORT INTERFERING RNA PRODUCTION TECHNOLOGIES

TABLE 15 (CONTINUED)

SHORT INTERFERING RNA EFFECTOR MOLECULE

DESIGN

Short Interfering RNA Effector … (Continued)

siRNA Design Goals

Off-target Effects

TABLE 16 TYPES OF OFF-TARGET EFFECTS

INDUSTRY STANDARDS FOR SHORT INTERFERING RNA

PERFORMANCE

POOLED SHORT INTERFERING RNAS

DELIVERY

DETECTION

mRNA Detection

TABLE 17 RNA DETECTION TECHNOLOGIES

Protein Detection

Functional Assays

Other Detection Strategies

SHORT INTERFERING RNA LENGTH RATIONALE

RNA INTERFERENCE IN RESEARCH TOOLS MARKETS

POST-GENOME ERA RESEARCH TRENDS

TABLE 18 POST GENOME RESEARCH LANDSCAPE

APPLICATIONS OF RNA INTERFERENCE AS A RESEARCH TOOL

TABLE 19 RNA INTERFERENCE APPLICATIONS AS A RESEARCH TOOL

GENE KNOCKDOWN

PATHWAY ANALYSIS

DRUG TARGET DISCOVERY AND VALIDATION

TABLE 20 RNA INTERFERENCE APPROACH TO IDENTIFY TIGHT JUNCTION PROTEIN TARGETS

FUNCTIONAL GENOMICS EXPERIMENTAL WORKFLOW

TABLE 21 FUNCTIONAL GENOMICS RESEARCH WORKFLOW AND RELATED RNA INTERFERENCE PRODUCTS

MICRO RNA FUNCTIONAL ANALYSIS EXPERIMENTAL

WORKFLOW

TECHNOLOGY NEEDS

TABLE 22 TECHNOLOGY NEEDS FOR RNA INTERFERENCE AS A RESEARCH TOOL

RNA INTERFERENCE IN DIAGNOSTICS

INTRODUCTION

TABLE 23 BIOMARKER COMPARISON

CORE SKILLS FOR MIRNA DIAGNOSTICS

TABLE 24 ENABLING TECHNOLOGIES FOR MICRO RNA DIAGNOSTICS DEVELOPMENT

IN VITRO DIAGNOSTICS DEVELOPMENT STAGES

TABLE 25 IN VITRO DIAGNOSTICS DEVELOPMENT PHASES

Biomarker Discovery

Assay Development

Clinical Validation

Regulatory Review and Approval

RNAI DIAGNOSTICS PIPELINE

TABLE 26 RNA INTERFERENCE DIAGNOSTICS PIPELINE

RNAi Diagnostics Pipeline (Continued)

RNAi Diagnostics Pipeline (Continued)

RNA INTERFERENCE IN AGRICULTURE

MARKET DRIVING FORCES

TABLE 27 DRIVING FORCES FOR RNA INTERFERENCE-BASED CROP PROTECTION

RNA INTERFERENCE-BASED INSECTICIDES

RNA INTERFERENCE-BASED CROP TRAITS

DEVELOPMENT OF A GENETICALLY MODIFIED SEED

TABLE 28 GENETICALLY MODIFIED SEED DEVELOPMENT PROCESS

RNA INTERFERENCE ADVANTAGES IN AGRICULTURE

APPLICATIONS

RNA INTERFERENCE THERAPEUTICS TECHNOLOGIES

INTRODUCTION

FIGURE 5 DRUG PLATFORMS

RNA INTERFERENCE THERAPY COMPARATIVE ADVANTAGES

TABLE 29 RNA INTERFERENCE THERAPY: COMPARATIVE ADVANTAGES

FIGURE 6 RNA INTERFERENCE IN DRUG DISCOVERY AND DEVELOPMENT

RNA INTERFERENCE THERAPEUTIC APPROACHES

TABLE 30 RNA INTERFERENCE THERAPEUTIC APPROACHES

SIRNA DRUG DEVELOPMENT PROCESS

FIGURE 7 SHORT INTERFERING RNA DRUG DEVELOPMENT PROCESS

RNA INTERFERENCE DELIVERY TECHNOLOGIES

FIGURE 8 RNA INTERFERENCE: LOCAL DELIVERY APPROACHES

FIGURE 9 RNA INTERFERENCE SYSTEMIC DELIVERY APPROACHES

TABLE 31 IN-VIVO VIRAL VECTOR TECHNOLOGIES COMPARED

TABLE 31 (CONTINUED)

TABLE 32 RNA INTERFERENCE DELIVERY TECHNOLOGY PLATFORMS IN CLINICAL TRIALS

KEY DEVELOPMENT NEEDS FOR RNA INTERFERENCE THERAPEUTICS

TABLE 33 RNA INTERFERENCE THERAPEUTICS KEY DEVELOPMENT NEEDS

KEY DEVELOPMENT NEEDS …(CONTINUED)

MICRO RNA THERAPEUTICS

RNA INTERFERENCE THERAPEUTICS PIPELINE

ANTISENSE BACKGROUND

TABLE 34 ANTISENSE OLIGO CLINICAL PIPELINE STATUS

TABLE 34 (CONTINUED)

RNA INTERFERENCE PIPELINE OVERVIEW

TABLE 35 RNA INTERFERENCE DEVELOPMENT AND CLINICAL

PIPELINE SUMMARY

TABLE 36 DISEASES TARGETED BY RNA INTERFERENCE THERAPEUTICS

TABLE 36 (CONTINUED)

PRE-CLINICAL RNAI PIPELINE

TABLE 37 RNA INTERFERENCE THERAPY PRE-CLINICAL PIPELINE STATUS

TABLE 37 (CONTINUED)

TABLE 37 (CONTINUED)

Alnylam

AlphaGen

Benitec

Calando

Genable

Genesis

Genecare

Intradigm

Nastech

Nucleonics

Opko Health

Protiva

Quark Pharmaceuticals

Rosetta Genomics

Santaris

Silence Therapeutics

SirnaSense

Tacare

Targeted Genetics

TransGenex

RNAI CLINICAL PIPELINE

TABLE 38 RNA INTERFERENCE THERAPY CLINICAL PIPELINE STATUS

Allergan

Alnylam

Antigen Express

Benitec

Nucleonics

Opko Health

Quark Pharmaceuticals

Pfizer

RNA INTERFERENCE THERAPEUTICS DISEASE OVERVIEWS

INTRODUCTION

OPHTHALMIC DISEASES

Introduction

Epidemiology

TABLE 39 AMD GROWTH DRIVING FORCES

Existing and Emerging Therapies

TABLE 40 CLINICAL DEVELOPMENT PIPELINE FOR AMD

Existing and Emerging … (Continued)

Challenges for Existing and Emerging Therapies

TABLE 41 COMPARISON OF BEVASIRANIB, LUCENTIS AND MACUGEN

RESPIRATORY SYNCYTIAL VIRUS

Epidemiology

Existing and Emerging Therapies

TABLE 42 RSV DRUG PIPELINE

TABLE 42 (CONTINUED)

Treatment Segment

Prevention Segment

Challenges for Existing and Emerging Therapies

INFLUENZA

Epidemiology

Existing and Emerging Therapies

Limitations of Existing and Emerging Therapies

HEPATITIS C VIRUS (HCV)

Epidemiology

Existing and Emerging Therapies

Limitations of Existing and Emerging Therapies

HEPATITIS B VIRUS (HBV)

Epidemiology

Existing and Emerging Therapies

Limitations of Existing and Emerging Therapies

ACUTE RENAL FAILURE

Epidemiology

Existing Therapies

Limitations of Existing Therapies

ONCOLOGY

HYPERLIPIDEMIA

RNA INTERFERENCE MARKETS

GROWTH DRIVING FORCES

TABLE 43 PRIMARY FORCES DRIVING RNA INTERFERENCE GROWTH

FUNDING FOR LIFE SCIENCE RESEARCH

NEW DISCOVERIES IN GENOMICS AND NANOTECHNOLOGIES

NEED FOR EFFICIENT DRUG DISCOVERY AND DEVELOPMENT

NEED FOR PLATFORMS THAT CAN ACCESS ‘UNDRUGGABLE’ TARGETS

GROWTH IN PERSONALIZED MEDICINES

NEED FOR ENVIRONMENTALLY FRIENDLY

AGROCHEMICALS

RNA INTERFERENCE OVERALL MARKET

TABLE 44 GLOBAL VALUE OF RNA INTERFERENCE MARKET BY MARKET SEGMENT, THROUGH 2013 ($ MILLIONS)

TABLE 45 GLOBAL VALUE OF RNA INTERFERENCE MARKET BY GEOGRAPHY, THROUGH 2013 ($ MILLIONS)

RNAI RESEARCH TOOLS MARKET

TABLE 46 GLOBAL VALUE OF RNA INTERFERENCE RESEARCH TOOLS MARKET BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS)

TABLE 47 GLOBAL VALUE OF SYNTHETIC SHORT INTERFERING RNA MARKET BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS)

TABLE 48 GLOBAL VALUE OF RNA INTERFERENCE DETECTION REAGENTS/KITS, BY TECHNOLOGY, THROUGH 2013 ($ MILLIONS)

TABLE 49 GLOBAL VALUE OF RNA INTERFERENCE DETECTION REAGENTS/KITS, BY BIOLOGICAL TARGET, THROUGH 2013 ($ MILLIONS)

TABLE 50 GLOBAL VALUE OF RNA INTERFERENCE RESEARCH TOOLS, BY GEOGRAPHY, THROUGH 2013 ($ MILLIONS)

RNAI DIAGNOSTICS MARKET

TABLE 51 GLOBAL VALUE OF RNA INTERFERENCE DIAGNOSTICS MARKET, BY TYPE, THROUGH 2013 ($ MILLIONS)

TABLE 52 GLOBAL VALUE OF RNA INTERFERENCE DIAGNOSTICS MARKET, BY INDICATION, THROUGH 2013 ($ MILLIONS)

TABLE 53 GLOBAL VALUE OF RNA INTERFERENCE DIAGNOSTICS MARKET, BY GEOGRAPHY, THROUGH 2013 ($ MILLIONS)

RNA INTERFERENCE THERAPEUTICS MARKET

TABLE 54 RNA INTERFERENCE GLOBAL AVAILABLE DRUG MARKET, THROUGH 2013 ($ MILLIONS)

TABLE 55 RNA INTERFERENCE THERAPEUTICS CLINICAL AND LATE STAGE PRECLINICAL PROJECTS AND MARKET ASSUMPTIONS

RNA INTERFERENCE THERAPEUTICS … (CONTINUED)

TABLE 56 GLOBAL VALUE OF RNA INTERFERENCE DRUG MARKET, BY CLASS, THROUGH 2013 ($ MILLIONS)

TABLE 57 GLOBAL VALUE OF RNA INTERFERENCE OPHTHALMIC DRUG MARKET, THROUGH 2013 ($ MILLIONS)

TABLE 58 GLOBAL VALUE OF RNA INTERFERENCE VIRAL DISEASE DRUG MARKET BY INDICATION, THROUGH 2013 ($ MILLIONS)

RNA INTERFERENCE THERAPEUTICS … (CONTINUED)

RNA INTERFERENCE THERAPEUTICS … (CONTINUED)

TABLE 59 GLOBAL VALUE OF RNA INTERFERENCE CANCER DRUG MARKET BY INDICATION, THROUGH 2013 ($ MILLIONS)

TABLE 60 GLOBAL VALUE OF RNA INTERFERENCE DRUG MARKET BY GEOGRAPHY, THROUGH 2013 ($ MILLIONS)

TABLE 61 GLOBAL VALUE OF OVERALL RNA INTERFERENCE DRUG MARKET BY DELIVERY TECHNOLOGY, THROUGH 2013 ($ MILLIONS)

RNA INTERFERENCE THERAPEUTICS … (CONTINUED)

RNA INTERFERENCE AGRICULTURAL MARKETS

TABLE 62 GLOBAL VALUE OF RNA INTERFERENCE AGRICULTURAL MARKET, BY PRODUCT, THROUGH 2013 ($ MILLIONS)

TABLE 63 GLOBAL VALUE OF RNA INTERFERENCE AGRICULTURAL MARKET, BY GEOGRAPHY, THROUGH 2013 ($ MILLIONS)

RNA INTERFERENCE COMPETITOR LANDSCAPE

INTRODUCTION

R&D TOOLS

DIAGNOSTICS

TABLE 64 RNA INTERFERENCE DIAGNOSTICS COMPANY RELATIVE STRATEGIC POSITION

Diagnostics (Continued)

THERAPEUTICS

Company Strategic Positions

TABLE 65 RNA INTERFERENCE THERAPEUTIC COMPANY RELATIVE STRATEGIC POSITION

TABLE 65 (CONTINUED)

TABLE 66 THERAPEUTIC RNA INTERFERENCE COMPETITOR STRATEGIC MARKET POSITION

Big Pharma Strategic Alliances with RNAi Companies

TABLE 67 BIG PHARMA RNA INTERFERENCE STRATEGIC ALLIANCES

TABLE 67 (CONTINUED)

Big Pharma Strategic …(Continued)

RNAI PATENTS

BASIC RNAI PATENT TYPES

TABLE 68 BASIC RNA INTERFERENCE PATENT TYPES

MICRO RNA PATENTS

TABLE 69 KEY STEPS FOR PATENTING MICRO RNA

RNA INTERFERENCE PATENT LANDSCAPE

TABLE 70 RNA INTERFERENCE CORE PATENT STRATEGIES

RNA INTERFERENCE CORE PATENT ESTATES

TABLE 71 RNA INTERFERENCE CORE PATENT ESTATES

TABLE 71 (CONTINUED)

MELLO & FIRE, ISSUED JANUARY 2004

CROOKE (ISSUED 1999 AND 2000)

TUSCHL I (APPLICATION PENDING) AND TUSCHL II

(ISSUED JULY 2006) PATENT ESTATES

TABLE 72 TUSCHL I AND TUSCHL II CLAIMS

KREUTZER-LIMMER (K-L) PATENT (ISSUED 2002)

TABLE 73 COMPARISON OF TUSCHL AND K-L PATENT ESTATES BENITEC (ISSUED JUNE 2003, PULLED FOR REEXAMINATION)

MICRO RNA PATENTS

TABLE 74 ACCESS TO VALIDATED HUMAN MICRO RNA

APPROACHES FOR WORKING AROUND THE CORE PATENTS

RNA INTERFERENCE PATENT LITIGATION STATUS

TABLE 75 RECENT RNA INTERFERENCE IP COURT ACTIVITY

INTELLECTUAL PROPERTY STRATEGIES OF SELECTED RNA

INTERFERENCE COMPANIES

ALNYLAM

TABLE 76 RECENT ALNYLAM PATENT ACTIVITY

SILENCE THERAPEUTICS

BENITEC

ISIS PHARMACEUTICALS

ROSETTA GENOMICS

Rosetta Genomics (Continued)

COMPANY PROFILES

454 LIFE SCIENCES

ACTIGENICS S.A.

AGILENT TECHNOLOGIES, INC.

ALLERGAN, INC

ALNYLAM PHARMACEUTICALS

TABLE 77 ALNYLAM SELECTED COMPANY DEALS

TABLE 78 ALNYLAM IP STRATEGY

TABLE 79 ALNYLAM KEY COLLABORATIONS

TABLE 79 (CONTINUED)

ALNYLAM PHARMACEUTICALS (CONTINUED)

TABLE 80 ALNYLAM PRODUCT PIPELINE SUMMARY

ALPHAGEN COMPANY LIMITED

AMAXA AG

ANTIGEN EXPRESS, INC

APPLIED BIOSYSTEMS

ASTRAZENECA

ASURAGEN, INC.

B-BRIDGE INTERNATIONAL INC.

BENITEC LIMITED

BIOCAT GMBH

BIOCHAIN INSTITUTE INC.

BIOGNOSTIK GMBH

BIONEER CORPORATION

BIO-RAD LABORATORIES

CALANDO PHARMACEUTICALS INC

TABLE 81 CALANDO LICENSES

CEPHEID

CEQUENT PHARMACEUTICALS, INC

CENIX BIOSCIENCE GMBH

CLINICAL DATA INC

CLONTECH

COMBIMATRIX CORPORATION

DEVGEN NV

DEVGEN NV (CONTINUED)

DHARMACON INC.

DNAVISION SA

EUROGENTEC S.A

EXIQON A/S

FEBIT BIOTECH GMBH

F. HOFFMANN-LA ROCHE LTD

GALAPAGOS NV

GENABLE TECHNOLOGIES LIMITED

GENECARE RESEARCH INSTITUTE CO.

GENECOPOEIA, INC.

GENEDESIGN, INC

GENE LINK, INC.

GENESERVICE LIMITED

GENOSENSOR CORPORATION

GENESIS RESEARCH & DEVELOPMENT CORPORATION

LIMITED

GENOMICA S.A.U

GENOWAY

GENLANTIS

GENSCRIPT CORPORATION

GENTA INC.

IDERA PHARMACEUTICALS INC.

IMAGENES GMBH

IMGENEX CORP

IMMUTHES THERAPEUTICS LTD

INTEGRATED DNA TECHNOLOGIES

INTRADIGM

INVITROGEN CORPORATION

INVIVOGEN

ISIS PHARMACEUTICALS, INC

LENTIGEN CORPORATION

MERCK & CO. INC.

MIRUS BIO CORPORATION

NASTECH PHARMACEUTICALS

NASTECH PHARMACEUTICALS (CONTINUED)

NOVOSOM AG

NUCLEONICS, INC.

NUCLEONICS, INC. (CONTINUED)

NUCLEIS

OLIGOENGINE

OPEN BIOSYSTEMS

OPKO HEALTH, INC

ORIGENE TECHNOLOGIES, INC.

OZ BIOSCIENCES

PHYTOVATION BV

POLYPLUS TRANSFECTION SA

PRONAI THERAPEUTICS, INC.

PROTIVA BIOTHERAPEUTICS

PROTIVA BIOTHERAPEUTICS (CONTINUED)

QIAGEN GMBH

QUARK BIOTECH, INC

TABLE 82 QUARK DEVELOPMENT PIPELINE

REGULUS PHARMACEUTICALS

RNAX GMBH

ROSETTA GENOMICS, LTD

ROSETTA GENOMICS, LTD. (CONTINUED)

THE LEAD DIAGNOSTICS PRODUCTS ARE TUMOR

CLASSIFICATION

Differentiation between Adeno- vs Squamous Cell

Cancers that are Poorly Differentiated, Mixed or Pure,

On Paraffin Samples.

Differentiate between Lung Cancer and Mesothelioma.

CUP Classification

CUP Classification (Continued)

TABLE 83 ROSETTA GENOMICS STRATEGIC PARTNERSHIPS

RXI PHARMACEUTICALS

TABLE 84 RXI PHARMACEUTICALS PATENT POSITION SUMMARY

SANTARIS PHARMA A/S

SIGMA ALDRICH

SILENCE THERAPEUTICS PLC

SILENCE THERAPEUTICS PLC. (CONTINUED)

SILENCE THERAPEUTICS PLC. (CONTINUED)

TABLE 85 SILENCE THERAPEUTICS RNA INTERFERENCE DRUG PIPELINE

SIRNASENSE

STARPHARMA HOLDINGS LIMITED

TACERE THERAPEUTICS, INC

TACERE THERAPEUTICS, INC. (CONTINUED)

TACONICARTEMIS GMBH

TEKMIRA PHARMACEUTICALS CORPORATION

TOLEROTECH INC.

TRANSAT

TRANSGENEX NANABIOTECH

WELGEN CORPORATION

LIST OF TABLES

SUMMARY TABLE GLOBAL VALUE OF RNA INTERFERENCE

MARKET BY MARKET SEGMENT, THROUGH 2013 ($ MILLIONS)

TABLE 1 POST GENOME ENABLING TOOLS

TABLE 2 NEW PARADIGM OF RNA INTERFERENCE

TABLE 3 GLOBAL VALUE OF RNA INTERFERENCE MARKET BY

MARKET SEGMENT, THROUGH 2013 ($ MILLIONS)

TABLE 4 GLOBAL VALUE OF RNA INTERFERENCE RESEARCH TOOLS

MARKET BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS)

TABLE 5 GLOBAL VALUE OF RNA INTERFERENCE DRUG MARKET,

BY CLASS, THROUGH 2013 ($ MILLIONS)

TABLE 6 PRIMARY FORCES DRIVING RNA INTERFERENCE GROWTH

TABLE 7 KEY ANTISENSE CONTRIBUTIONS TO RNA INTERFERENCE

TABLE 8 BASIC STEPS IN PROTEIN PRODUCTION

TABLE 9 COMPARISON OF RNA INTERFERENCE AND ANTISENSE

OLIGO TECHNOLOGIES

TABLE 10 SHORT INTERFERING, SHORT HAIRPIN, AND MICRO RNA

VERSUS OLIGO ANTISENSE TECHNOLOGIES

TABLE 11 RNA INTERFERENCE HISTORY

TABLE 12 ANTISENSE TECHNOLOGY PLATFORMS

TABLE 13 NEAR TERM RNA INTERFERENCE COMMERCIAL

APPLICATIONS

TABLE 14 COMPARISON OF METHODS FOR PRODUCING SHORT

INTERFERING RNA

TABLE 15 COMPARISON OF SYNTHETIC AND PLASMID SHORT

INTERFERING RNA PRODUCTION TECHNOLOGIES

TABLE 16 TYPES OF OFF-TARGET EFFECTS

TABLE 17 RNA DETECTION TECHNOLOGIES

TABLE 18 POST GENOME RESEARCH LANDSCAPE

TABLE 19 RNA INTERFERENCE APPLICATIONS AS A RESEARCH

TOOL

TABLE 20 RNA INTERFERENCE APPROACH TO IDENTIFY TIGHT

JUNCTION PROTEIN TARGETS

TABLE 21 FUNCTIONAL GENOMICS RESEARCH WORKFLOW AND

RELATED RNA INTERFERENCE PRODUCTS

TABLE 22 TECHNOLOGY NEEDS FOR RNA

INTERFERENCE AS A RESEARCH TOOL

TABLE 23 BIOMARKER COMPARISON

TABLE 24 ENABLING TECHNOLOGIES FOR MICRO RNA

DIAGNOSTICS DEVELOPMENT

TABLE 26 RNA INTERFERENCE DIAGNOSTICS PIPELINE

TABLE 27 DRIVING FORCES FOR RNA INTERFERENCE-BASED CROP

PROTECTION

TABLE 28 GENETICALLY MODIFIED SEED DEVELOPMENT PROCESS

TABLE 29 RNA INTERFERENCE THERAPY: COMPARATIVE

ADVANTAGES

TABLE 30 RNA INTERFERENCE THERAPEUTIC APPROACHES

TABLE 31 IN-VIVO VIRAL VECTOR TECHNOLOGIES COMPARED

TABLE 32 RNA INTERFERENCE DELIVERY TECHNOLOGY

PLATFORMS IN CLINICAL TRIALS

TABLE 33 RNA INTERFERENCE THERAPEUTICS KEY DEVELOPMENT

NEEDS

TABLE 34 ANTISENSE OLIGO CLINICAL PIPELINE STATUS

TABLE 35 RNA INTERFERENCE DEVELOPMENT AND CLINICAL

PIPELINE SUMMARY

TABLE 36 DISEASES TARGETED BY RNA INTERFERENCE

THERAPEUTICS

TABLE 37 RNA INTERFERENCE THERAPY PRE-CLINICAL PIPELINE

STATUS

TABLE 38 RNA INTERFERENCE THERAPY CLINICAL PIPELINE

STATUS

TABLE 39 AMD GROWTH DRIVING FORCES

TABLE 40 CLINICAL DEVELOPMENT PIPELINE FOR AMD

TABLE 41 COMPARISON OF BEVASIRANIB, LUCENTIS AND

MACUGEN

TABLE 42 RSV DRUG PIPELINE

TABLE 43 PRIMARY FORCES DRIVING RNA INTERFERENCE

GROWTH

TABLE 44 GLOBAL VALUE OF RNA INTERFERENCE MARKET BY

MARKET SEGMENT, THROUGH 2013 ($ MILLIONS)

TABLE 45 GLOBAL VALUE OF RNA INTERFERENCE MARKET BY

GEOGRAPHY, THROUGH 2013 ($ MILLIONS)

TABLE 46 GLOBAL VALUE OF RNA INTERFERENCE RESEARCH

TOOLS MARKET BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS)

TABLE 47 GLOBAL VALUE OF SYNTHETIC SHORT INTERFERING

RNA MARKET BY PRODUCT TYPE, THROUGH 2013 ($ MILLIONS)

TABLE 48 GLOBAL VALUE OF RNA INTERFERENCE DETECTION

REAGENTS/KITS, BY TECHNOLOGY, THROUGH 2013 ($ MILLIONS)

TABLE 49 GLOBAL VALUE OF RNA INTERFERENCE DETECTION

REAGENTS/KITS, BY BIOLOGICAL TARGET, THROUGH 2013

($ MILLIONS)

TABLE 50 GLOBAL VALUE OF RNA INTERFERENCE RESEARCH

TOOLS, BY GEOGRAPHY, THROUGH 2013 ($ MILLIONS)

TABLE 51 GLOBAL VALUE OF RNA INTERFERENCE DIAGNOSTICS

MARKET, BY TYPE, THROUGH 2013 ($ MILLIONS)

TABLE 52 GLOBAL VALUE OF RNA INTERFERENCE DIAGNOSTICS

MARKET, BY INDICATION, THROUGH 2013 ($ MILLIONS)

TABLE 53 GLOBAL VALUE OF RNA INTERFERENCE DIAGNOSTICS

MARKET, BY GEOGRAPHY, THROUGH 2013 ($ MILLIONS)

TABLE 54 RNA INTERFERENCE GLOBAL AVAILABLE DRUG MARKET,

THROUGH 2013 ($ MILLIONS)

TABLE 55 RNA INTERFERENCE THERAPEUTICS CLINICAL AND

LATE STAGE PRECLINICAL PROJECTS AND MARKET

ASSUMPTIONS

TABLE 56 GLOBAL VALUE OF RNA INTERFERENCE DRUG MARKET,

BY CLASS, THROUGH 2013 ($ MILLIONS)

TABLE 57 GLOBAL VALUE OF RNA INTERFERENCE OPHTHALMIC

DRUG MARKET, THROUGH 2013 ($ MILLIONS)

TABLE 58 GLOBAL VALUE OF RNA INTERFERENCE VIRAL DISEASE

DRUG MARKET BY INDICATION, THROUGH 2013 ($ MILLIONS)

TABLE 59 GLOBAL VALUE OF RNA INTERFERENCE CANCER DRUG

MARKET BY INDICATION, THROUGH 2013 ($ MILLIONS)

TABLE 60 GLOBAL VALUE OF RNA INTERFERENCE DRUG MARKET

BY GEOGRAPHY, THROUGH 2013 ($ MILLIONS)

TABLE 61 GLOBAL VALUE OF OVERALL RNA INTERFERENCE DRUG

MARKET BY DELIVERY TECHNOLOGY, THROUGH 2013

($ MILLIONS)

TABLE 62 GLOBAL VALUE OF RNA INTERFERENCE AGRICULTURAL

MARKET, BY PRODUCT, THROUGH 2013 ($ MILLIONS)

TABLE 63 GLOBAL VALUE OF RNA INTERFERENCE AGRICULTURAL

MARKET, BY GEOGRAPHY, THROUGH 2013 ($ MILLIONS)

TABLE 64 RNA INTERFERENCE DIAGNOSTICS COMPANY RELATIVE

STRATEGIC POSITION

TABLE 65 RNA INTERFERENCE THERAPEUTIC COMPANY RELATIVE

STRATEGIC POSITION

TABLE 66 THERAPEUTIC RNA INTERFERENCE COMPETITOR

STRATEGIC MARKET POSITION

TABLE 67 BIG PHARMA RNA INTERFERENCE STRATEGIC

ALLIANCES

TABLE 68 BASIC RNA INTERFERENCE PATENT TYPES

TABLE 69 KEY STEPS FOR PATENTING MICRO RNA

TABLE 70 RNA INTERFERENCE CORE PATENT STRATEGIES

TABLE 71 RNA INTERFERENCE CORE PATENT ESTATES

TABLE 72 TUSCHL I AND TUSCHL II CLAIMS

TABLE 73 COMPARISON OF TUSCHL AND K-L PATENT ESTATES

TABLE 74 ACCESS TO VALIDATED HUMAN MICRO RNA

TABLE 75 RECENT RNA INTERFERENCE IP COURT ACTIVITY

TABLE 76 RECENT ALNYLAM PATENT ACTIVITY

TABLE 77 ALNYLAM SELECTED COMPANY DEALS

TABLE 78 ALNYLAM IP STRATEGY

TABLE 79 ALNYLAM KEY COLLABORATIONS

TABLE 80 ALNYLAM PRODUCT PIPELINE SUMMARY

TABLE 81 CALANDO LICENSES

TABLE 82 QUARK DEVELOPMENT PIPELINE

TABLE 83 ROSETTA GENOMICS STRATEGIC PARTNERSHIPS

TABLE 84 RXI PHARMACEUTICALS PATENT POSITION SUMMARY

TABLE 85 SILENCE THERAPEUTICS RNA INTERFERENCE DRUG

PIPELINE

LIST OF FIGURES

SUMMARY FIGURE GLOBAL VALUE OF RNA INTERFERENCE

MARKET BY MARKET SEGMENT, 2006-2013 ($ MILLIONS)

FIGURE 1 ROLE OF MESSENGER RNA IN PROTEIN PRODUCTION

FIGURE 2 RNA INTERFERENCE PROCESS

FIGURE 3 MICRO RNA BIOGENESIS

FIGURE 4 RNA INTERFERENCE RESEARCH TOOLS PRODUCTS

FIGURE 5 DRUG PLATFORMS

FIGURE 6 RNA INTERFERENCE IN DRUG DISCOVERY AND

DEVELOPMENT

FIGURE 7 SHORT INTERFERING RNA DRUG DEVELOPMENT

PROCESS

FIGURE 8 RNA INTERFERENCE: LOCAL DELIVERY APPROACHES

FIGURE 9 RNA INTERFERENCE SYSTEMIC DELIVERY APPROACHES

Abstract

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