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

Table of Contents

• 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)

• 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)

• 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 16TYPES 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

• 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

• 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)

• 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

• 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

• 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)

• 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)

• 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 RE-EXAMINATION).
  • 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)

• 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