MicroRNAs: Commercial Products on the Horizon

SUMMARY

With the first diagnostics set to debut within a year, the new research and development field of microRNAs is beginning to reveal its potential. This new report establishes a baseline for observing microRNAs' maturation, including assessments of:

• The science and analysis of first-generation microRNA commercial applications
• The early adaptors and where they are heading with this emerging technology
• Clinical applications, which will begin in oncology, followed by infectious diseases, neurology, metabolic disorders, and cardiovascular diseases
• The youthfulness of the field of microRNA
• The status of the field, including promises and caveats, companies involved, and pertinent patents and intellectual property
• Companies that are either developing microRNAs as clinical tools, investigating microRNAs in basic research, or supplying reagents, kits, microarrays, bioinformatics tools, and other essentials

The report also includes interviews with experts at some of the companies involved, including those devoted to microRNAs, those at which microRNAs comprise part of the portfolio, and companies that enable the others. In addition, results of a quantitative online survey of individuals involved in microRNA R&D are included.

MicroRNAs are a class of small, nonprotein-encoding endogenous RNA molecules that exert powerful effects on gene expression by destabilizing transcription and/or repressing translation of target messenger RNAs. They have profound functions, which scientists are just beginning to tease out. More than 5,000 microRNAs have been identified.

The human genome sequence encodes hundreds to thousands of microRNAs, and they regulate at least a third of the protein-encoding genes. MicroRNAs' malfunction may lie behind many illnesses.

From an initial unheralded description in 1993 and then a set of stellar foundation papers around the turn of the millennium, microRNAs have been hurtling toward commercialization ever since. Recognition of the importance of microRNAs catalyzed development of tools and technologies to ease their investigation. And as more has been learned, bioinformatics prediction tools have evolved. The many kits developed for working with microRNAs have made possible the debut of the first clinical products in under a decade from the recognition of their discovery.

TABLE OF CONTENTS

Chapter 1 INTRODUCTION

• 1.1. State of the Science
• 1.2. Why Did MicroRNAs Escape Notice?
• 1.3. The Discovery of MicroRNAs
  • Enter RNA Interference
  • The Initial Papers
  • Defining and Describing MicroRNAs
    • Criteria
    • Genomic Addresses
    • Abundance and Diversity
• 1.4. Mechanisms and Targets
  • MicroRNAs in Plants and Animals
  • From Precursor to Mature MicroRNA
  • Targets
• 1.5. MicroRNA Sequence Variation
• 1.6. Evolutionary Significance
• 1.7. Analysis

Chapter 2 THE TECHNOLOGICAL LANDSCAPE

• 2.1. Collecting and Profiling MicroRNAs
  • The Workflow: Isolate, Enrich, Detect, Quantify, and Analyze
  • Arrays and Assays
  • Customized Microarrays
• 2.2. Inhibiting MicroRNAs
  • Locked Nucleic Acid Modified Antisense Oligonucleotides
  • Morpholinos
  • Antagomirs
  • MicroRNA Sponges
• 2.3. Databases and Computational Tools
  • MiRBase
  • Computational Tools (In Silico Predictions)

Chapter 3 CLINICAL APPLICATIONS

• 3.1. Oncology
  • Onco-miRs and Tumor-Suppressor MicroRNAs
  • let-7 Led the Way
  • Further Evidence Linking MicroRNAs to Cancer
  • Clinical Applications of MicroRNAs in Cancer
    • Diagnosis
    • Therapeutics
• 3.2. Infectious Disease
  • Cytomegalovirus (CMV)
  • Human Immunodeficiency Virus (HIV)
• 3.3. Neurological Disease
• 3.4. Cardiovascular Disease

Chapter 4 BASIC RESEARCH

• 4.1. Differentiation and Development
  • MicroRNA Control in Embryos
  • Role of MicroRNAs in Aging
• 4.2. Evolution

Chapter 5 COMMERCIAL OUTLOOK

• 5.1. Promises and Caveats
• 5.2. Commercialization
  • Companies Devoted Exclusively to MicroRNAs
  • RNAi Companies Developing MicroRNAs
  • Spinouts from 1 or More Companies
  • Big Pharma
  • Traditional Suppliers of Reagents and Kits
• 5.3. Patent and Intellectual Property Issues
  • Recent MicroRNA Patents
  • The RNAi Legacy
• 5.4. The Future

Chapter 6 EXPERT INTERVIEWS

• Christoper Adams, PhD, Research Area Manager, Research & Development/Epigenetics, Invitrogen, Carlsbad, CA
• Dalia Cohen, PhD, Executive Vice President, Head of Global Research and Development, Rosetta Genomics, Rehovot, Israel and North Brunswick, NJ
• Iain Russell, PhD, Product Manager, TaqMan MicroRNA Assays, Applied Biosystems, Foster City, CA
• Frank Slack, PhD, Associate Professor of Molecular, Cellular and Developmental Biology, Yale University, New Haven, CT
• Phillip D. Zamore, PhD, Gretchen Stone Cook Professor of Biomedical Sciences, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, MA

Chapter 7 SELECTED COMPANY PROFILES

• Agilent Technologies
• Asuragen
• Cepheid and Actigenics-Cepheid
• Dharmacon Products (part of Thermo Fisher Scientific)
• Exiqon
• Invitrogen
• Luminex
• QIAGEN
• Regulus Therapeutics
• Rosetta Genomics
• Santaris Pharma

Appendix

• INSIGHT PHARMA REPORTS MicroRNA SURVEY-DECEMBER 2007

Glossary

• References
• Company Index with Web Addresses