Synthetic Biology: An Emerging Tool for Drug Discovery and Production

SUMMARY

Introduction

Lying at the interface of biology and engineering, synthetic biology represents a new discipline emphasizing an engineering approach to building biological systems from components. Already, simple synthetic devices such as biological “clocks” have been created from “parts” such as protein coding and regulatory DNA sequences. These and other devices are helping researchers engineer the production and discovery of terpenoid and polyketide drugs. Although primarily practiced in academic institutions concentrated in the major biotech centers of the United States, synthetic biology is now attracting venture capitalists as well as major grants from nonprofi t foundations and partnerships with such well-established pharmaceutical companies as Roche and Pfi zer. This revolutionary technology holds the promise to become a powerful commercial tool for small-molecule drug discovery and development.

Get the Answers You Need to Shape Your Strategy

• Although still an emerging fi eld, synthetic biology has already allowed the launch of several start-up companies. Several of these young companies are focusing on the use of synthetic biology in the development and discovery of drugs. Which companies are these, and on which drugs are these companies focusing their research efforts?
• A key concept in synthetic biology is the development of an inventory of modular biological “parts” that can be used in constructing synthetic biology devices and systems. Leaders in synthetic biology would like to standardize these parts so that they could be easily shared among researchers in laboratories throughout the world. What steps has the synthetic biology research community taken to begin the process of creating and sharing standardized parts?
• The ability of researchers to produce synthetic versions of pathogenic viruses may enable the production of inactive synthetic versions of these viruses for use as vaccines. Which viruses have researchers already successfully synthesized, and how have recent studies of these viruses led them to understand ways of potentially abolishing the virus's transmissibility?
• In June 2007, leaders of a group of DNA synthesis companies joined with FBI offi cials to publish a plan addressing concerns that potentially dangerous synthetic biology techniques might fall into the hands of terrorists. What plan did the FBI and DNA synthesis companies suggest to ward off potential threats associated with bioterrorism?
• Most of the scientifi c literature in synthetic biology reports construction of relatively simple synthetic biology devices by academic researchers. What do researchers hope to gain by constructing these simple devices?

Scope

• Introduction to synthetic biology: defi nition and goals; purposes and applications; relationship to systems biology.
• Precursors: genetic engineering; recombinant DNA technology; DNA synthesis and sequencing.
• Creating the new discipline: the core academic community; the international Synthetic Biology conference; the iGEM competition.
• Modular parts for engineering biological systems: “biobricks,” “chassis,” and minimal cells.
• Advances in DNA sequencing and synthesis technologies: reducing the cost of DNA sequencing; whole viral genomes; methods for synthesizing large DNA molecules; commercial suppliers of genetic constructs.
• Metabolic engineering: goals of pharmaceutical metabolic engineering; synthesis and discovery of drugs in the terpenoid and polyketide classes.
• Synthetic viral genomes: applications to vaccines and therapies; the 1918 infl uenza virus genome; the potential for novel vaccination strategies.
• Ethical, safety, and policy issues: comparisons with the birth of recombinant DNA technology; bioterrorism; a plan for self-regulation; patent issues.
• Profi les of synthetic biology companies: Amyris Biotechnologies, Biotica Technology, Blue Heron Biotechnology, Codon Devices, Kosan Biosciences, Synthetic Genomics.
• Outlook: the challenge of building synthetic biology devices; venture capital, foundation funding, and partnerships between start-up synthetic biology companies and established pharmaceutical companies; expanding commercial synthesis of large DNA constructs; the potential for more stringent governmental regulation.

TABLE OF CONTENTS

• Executive Summary
  • Strategic Considerations
  • Stakeholder Implications
• Introduction to Synthetic Biology
• Genetic Engineering: Precursor of Synthetic Biology
• Creating a New Discipline
  • The Core Academic Synthetic Biology Community
  • The International Genetically Engineered Machine (iGEM) Competition
• Applications of Synthetic Biology
• Modular Parts for Engineering Biological Systems
  • Biobricks
  • Chassis and the Minimal Cell
• Advances in DNA Sequencing and Synthesis Technologies
  • DNA Sequencing
  • DNA Synthesis
  • Suppliers of Biological Parts
• Construction of Synthetic Biology Devices
  • Synthetic Biological Clocks
  • RNA Antiswitches
• Metabolic Pathway Engineering for Small-Molecule Drug Synthesis and Discovery
  • Terpenoids
  • Polyketides
• Applications of Synthetic Viral Genomes to Vaccines and Therapies
• Ethical, Safety, and Policy Issues
• Synthetic Biology Companies
  • Amyris Biotechnologies
  • Biotica Technology
  • Blue Heron Biotechnology
  • Codon Devices
  • Kosan Biosciences
  • Synthetic Genomics
• Outlook for Synthetic Biology

Tables

• 1. Select Institutions Hosting Synthetic Biology Programs and Participating Laboratories
• 2. Potential Near-Term Applications of Synthetic Biology
• 3. Examples of Drugs in Natural Products Classes of Interest in Metabolic Engineering
• 4. Select Synthetic Biology Companies

Figures

• 1. Simplifi ed Diagram of the Repressilator Device
• 2. Schematic Diagram of the RNA Antiswitch
• 3. Schematic Diagram of the Mevalonate Pathway for Synthesis of Terpenoids
• 4. Synthetic Pathway for Artemisinin
• Figure accompanying sidebar: An Operon Controlled by a Repressor

Sidebar

• Operons and Metabolic Engineering for Drug Production