Synthetic Biology - United Nations Office at GenevahttpAssets)/A39A32D6E2E6… · NSABB Reports on...

1 7/19/2012 | Life Technologies™ Proprietary and confidential

Synthetic Biology: Biosecurity in a Rapidly Emerging Field

Dr. Marcus Graf, PhD Director Operations SynBio

Co-founder & COO of Geneart AG (now part of Lifetechnologies)


IGSC represents >80% of Gene Synthesis Market

Division: Synthetic BiologyDivision: Synthetic Biology

Charter members


2000 2010

USG dual use research

policy + rDNAguidelines revision

USG dual use research

policy + rDNAguidelines revision

Syn Bio 1.0 @ MIT

Syn Bio 1.0 @ MIT

NSABB Reports on Synthetic Genomics, Oversight Framework, Synthetic Biology, 2006‐2010



Human Genome Project, 2003

Human Genome Project, 2003

2007‐2009Genomic transplantation, assembly of whole bacterial genome, interspecies genomic

transfer


transfer


transfer

Artemisin, 2006

In vitro synthesis of polio virus, 2002 BioBricksTM

Artemisin, 2006Artemisin, 2006

In vitro synthesis of polio virus, 2002

In vitro synthesis of polio virus, 2002 BioBricksTMBioBricksTM

2003

NSABB establishment

200420032003

NSABB establishment

2004

NSABB establishment

2004

2000Gene

Synthesis GenomeSynthesis

ATG ATC TGT CAC GCA GAG CTAATG ATC TGT CAC GCA GAG CTA

Synthetic biology – Commercial Synthesiskey events in the past


Design, Bioinformatic Processing and Online Ordering

www

Online design & instant ORDERING via the WEB


Highthroughput DNA Synthesis

> 10.000 oligonucleotidesper day

> 100.000 oligonucleotides per day

TODAY

TOMORROW


5kbp

500kbp

DNA Fragment Assembly in Routine Production

Mueller et al 2009


Reading the Sequence

>10.000 reads per day >100.000 reads per day

TODAY TOMORROW

CE

NGS

8 7/19/2012 | Life Technologies™ Proprietary and confidentialop

portu

nity

Balanced Discussion to Take Advantage of the Opportunities and Minimize Risks

Goals & Objectives:

1) To design and apply a common Protocol to screen both the sequences of synthetic gene orders, and the customers who place them.

2) To work together with governments and others concerned to promote the beneficial application of gene synthesis technology, and to safeguard biosecurity.

Abuse of technology for terrorism

Healthcare, renewable energy, basic research, …


The IGSC harmonized screening protocol is:In line with the US guidelines

Based on experience and existing screening processes of founding members

Compulsory for IGSC members

Publically available**http://www.genesynthesisconsortium.org/


Department of Health and Human ServicesSCREENING FRAMEWORK GUIDANCE OR PROVIDERS OF SYNTHETIC DOUBLE-STRANDED DNA

Following these guidance is voluntary

The cornerstones:• Screening of sequences• Screening of customer• Follow-up screening if above raises concerns• Proper record retention• Recommendations regarding screening software

The Guidance was developed, in light of providers’ existing protocols, to be implemented without unnecessary cost and to be globally extensible, both for U.S.-based providers operating abroad and for international providers

Providers of synthetic dsDNA have two overriding responsibilities in this context:• Providers should know to whom they are distributing a product • Providers should know if the product that they are synthesizing and distributing contains, in part or in

whole, a “sequence of concern”

Screening Framework Guidance, Summary

http://bioethics.gov/


BioSafety BioSecurity“Gene Technology Law“

wwwBL

AST

Sequence HostSequence Function

??

ok

Country CheckCustomer Check

check

SHIP

Critical Sequence List(AG list, CDC)

Common IGSC DB

A

M ok

A = automatedM = manual

ok

(9 PhDs) Molecular Biologists

Life Technologies(Customer Service)

ok

Sequence Check

atlas

DocumentationSite Inspections

Customs Regulation, Export Control

Overview on Biosecurity Screening


blast results• sequence (gi)• organism (taxID) • ...

NCBI Blast-Database15.868.259 DNA-sequences

17.282.984 Protein-sequences

Local Blast-Mirror

updated quarterly

Sequence of Interest

blastxblastpblastn

Evaluated Results• Sequence (gi)• Organism (taxID) • BIOSECURITY RESULT

BlacklistOrganism and Sequence

AG, BIS, DOC, DOS, EC, HHS, USDA

182 main TaxIDs(~4 M sequences)

8753 reference GIsalligned with threat levels

Whitelist Organisms299 sub TaxIDs

(~3 M sequences)

BIOSECURITYDATABASE

Database

integration

ManualReview

Screening Procedure – Workflow

Used by all members!


Scientific ReviewLife Technologies (A. Rusch)& IDT (R. Dawson)

• Organism (TaxID) • Sequence (GI)

Translation table of allrelated legal documents

to TaxID and GInumbers

31.527 entriescovering > 4 M

sequences(to date, quarterly

updates)

IGSCDATABASE

Australia Group(AG)

UK Dep. forBusiness Innovation &

Skills (BIS)

US Departmentof Commerce

(DOC)

US Departmentof State(DOS)

European Community

(EC)

US Dep. of Healthand Human Services

(HHS)

US Department of Agricutlure (USDA)

IGSC Database


Our Activities

Continuous improvement: screening methods, tools & sequence database

Proactive participation in policy/regulation development

Engage the entire Industry

Ensure we all have the same standards


Input from Governments desired

Expert Opinion – defining sequences of concern− Australian Group List names only organisms, not sequences

− Definition of “genes associated with pathogenicity“ leaves room for interpretation

Universal continuously updated screening database− Ideally maintained by the U.S. Government / EU and international

organizations

Provider and User certification


Thank You!

Synthetic Biology - United Nations Office at GenevahttpAssets)/A39A32D6E2E6… · NSABB Reports on...

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