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FLEXGene Repository. Platform. Universal Access. Scientific Excellence. Freedom to Operate. The FLEXGene Platform. FLEXGene. Scientific Excellence. Highest quality Gold standard Fully sequence verified Flexibility Genes rapidly moved to any protein expression vector

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The flexgene platform





Freedom to


The FLEXGene Platform


Scientific excellence
Scientific Excellence

Highest quality

  • Goldstandard

  • Fully sequence verified


  • Genes rapidly moved to any protein expression vector

  • Collections of genes moved simultaneously with ease

  • Enables high-throughput functional experiments


  • World class experts have vetted the technologies

  • Pilot studies confirmed robustness

    Research and Development

  • Continued effort to improve vectors and gene transfer

Universal access
Universal Access

Broad availability

  • Equal access to the entire community

  • Includes both clones andcloning methodology

  • Provides a level playing field

    Distribution strategy promotes access

  • Multiple reputable distributors

  • Third party quality control

    Public/private venture

  • Membership open to all

  • Garners the bestexperience from all sectors

Freedom to operate
Freedom to Operate

FLEXGene clones

  • No restrictions or reach through attached to clones

  • Assembled and distributed under NIH umbrella

    FLEXGene cloning methodology

  • Methodology available to everyone

  • Simple and open licensing structure

  • Available in perpetuity

Flexgene repository1

FLEXGene Repository

Organizational Plan

Flexgene organizational structure
FLEXGeneOrganizational Structure


Scientific Advisory Board

(Contributing Members)

NIH Foundation

Legal Committee

Administrative Staff


Communications and Public Relations



Clone Production

Sequencing site(s)

Distribution and Quality Control

Director bob strausberg
DirectorBob Strausberg

  • Full time position

    • CGAP

    • MGC

    • FLEXGene

  • Responsible for:

    • Managing the project

    • Ensuring that suppliers reach milestones

    • Overseeing budget

    • Enforcing standards

    • Driving and managing all key activities & processes

    • Communications & PR (with Harlow and LaBaer)

    • Governance

Scientific advisory board
Scientific Advisory Board

  • One representative per member organization

  • One class of membership

  • Responsible for:

    • Setting the scope and objectives

    • Approving the standards

    • Monitoring and guiding the operations

    • Defining future projects

Flexgene repository2

FLEXGene Repository

Scientific Plan


Scope of project

  • One representative version for each human gene

  • Project limited to producing master clones

    • Expression clones and proteins to be made by users

  • Two clones per gene: with and without stop codon

    Clone production

  • FLEXGene uses MGC clones as starting template

    • High quality template

    • Fully sequenced

    • Fewer cycles of PCR needed  higher fidelity

  • MGC has agreed to continue until all genes represented

  • Alternate splice forms, mutant collections, etc. considered for subsequent projects, e.g., FLEXGene II

  • Cloning system selection to be managed by independent blue ribbon panel

The flexgene concept i
The FLEXGene Concept-I

5’ Untranslated

Coding Region

3’ Untranslated


Precisely copy the coding region

Add recombination sites

Move to plasmid vector

Master clones

that populate

the repository

  • Precise coding region

  • No 5’ stop codons, 5’ or 3’ regulatory sequences

  • Ready for expression as native protein, NH2- or COOH-terminal fusions

The flexgene concept ii
The FLEXGene Concept-II


master clone

Move the insert by recombination to:

(Now a simple automated procedure)

Any expression vector (bacteria, yeast, mammalian, viral et al.)

Native protein


Amino-terminal fusions


Carboxy-terminal fusions


Amino- and carboxy-terminal fusions

Pilot Study

Project Scope

  • GOAL:

  • Direct comparison of cloning systems

  • Assess mutation rate during clone assembly

  • Used MGC clones as template for PCR

  • Same set of 384 genes are cloned in each system

  • Evaluate each system based on

    • Efficiency (hit rate)

    • Product quality (sequence)

    • Ease of use (for cloners and for end users)

    • Cost

Sequence Fidelity

Pilot Study

384 MGC clones converted to each of two systems

Pilot completed in 3 months

No significant differences between systems

768 clones have been fully sequenced:

  • 192 genes, 2 systems, 2 separate isolates each

  • Sequencing done to at least 1 in 10,000 accuracy

  • Average mutation rate ~1 error every 3700 bases

  • Concordance indicates <3% duplicates have same mutation

  • Combining the two systems:

  • average = 1 error in every 4-5 clones.

  • Flexgene repository3

    FLEXGene Repository

    Legal and Intellectual Property Strategy

    Legal issues addressed
    Legal Issues Addressed

    Organizational structure

    • Under NIH umbrella

    • FLEXGene membership open to all

    • Uniform cost of membership; no special payment terms

    • Cloning system recommendations by independent blue ribbon panel

      Intellectual property

    • Existing gene IP

    • Cloning system IP

    • No IP overhead added by FLEXGene

    Intellectual property existing gene ip
    Intellectual PropertyExisting Gene IP

    FLEXGene will:

    • Publish its plans broadly

    • Operate under the NIH umbrella

    • Not search for IP on individual genes

    • Provide a shrink wrap MTA: it is users’ responsibility to check IP on specific genes

    • Attach no IP to the clones

    Intellectual property cloning system
    Intellectual PropertyCloning System

    FLEXGene (through NIH) will request a contract from cloning system provider that:

    • Ensures that users will always be able to usetechnology

      • Perpetual license

      • Methods for producing reagents will be placed in escrow

    • Ensures that there are no limitations on the use of the clones added by cloning technology

    • Ensures that the cost will be the same for everyone

    • Encourages innovation by ensuring that third parties who develop new technologies can make them compatible with the system

    • Ensures that the price will not jump as soon as the contract is signed

    • Ensures that clones can be distributed by multiple distributors

    Flexgene repository4

    FLEXGene Repository

    Clone Distribution and Maintenance Strategy

    Maintenance and distribution overview
    Maintenance and DistributionOverview

    • Vital issue for FLEXGene

    • Production  Central Archive  Distributors

    • Multiple distributors is essential

      • Multiple distributors ensure competitive pricing

      • Multiple distributors ensure better quality control

    • FLEXGene will not dictate price

    • License to distribute may be contingent upon a minimum level of quality control

    • Oversight board established to monitor quality control

    • Distributors can be commercial or non-profit

    • Distributors must offer all FLEXGene clones for sale

    • Distributors cannot provide clones to another distributor for resale

    Maintenance and distribution distributor responsibilities
    Maintenance and DistributionDistributor Responsibilities

    Distributors must provide

    • Clones on a fair, equitable and confidential basis

    • E-mail or web-based help desk

    • Clone annotation – either locally or linked to FLEXGene

    • E-mail or web-based complaint system with record keeping

    • A published and accessible list of their products, services, prices, expected response times and guaranteed delivery times

    • A completed MTA from each customer

    • Feedback on aberrant clone identities to the central archive

      Each distributor can determine its distribution format

    • DNA, bacterial strain, or both

      Distributors can offer additional services for added value

    • Pre-made clone sets (cancer, kinase, etc.)

    • User-specified custom sets

    • Re-sequencing, T1 Phage testing, testing for cross-contamination

    Maintenance and distribution distribution oversight board
    Maintenance and DistributionDistribution Oversight Board

    The Distribution Oversight Board will:

    • Consist of 4-6 users

      • Academic, commercial and geographic representation

      • No conflicts of interest with distributors

      • Agree to maintain confidentiality

    • Review complaints about distributors semi-annually

      • Ensure adequate response and follow-up

      • Ensure measures established to improve systematic problems

    • Spot check distributors annually (Optional)

      • Order 100-200 clones

        • Monitor service quality and response times

        • Ensure clone viability

        • Confirm clone quality by sequencing

      • Help to identify problems early, before complaints come in

    • Continue to operate even after production is completed

    Maintenance and distribution distributor qualifications
    Maintenance and DistributionDistributor Qualifications

    Experiencedistributing clones on a fee basis

    • Evidence of quality service

    • Positive customer references

      Existing infrastructure

    • For clone storage

    • For distribution

    • For testing

      • DNA Sequencing

      • Contamination monitoring

        Ability to provide annotation

    • Electronically

    • Enclosed with shipped parcel of clones