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The Medusa™ Sequencer: A DNA or RNA Sequencing Machine the Size of a Molecule

Description of Invention:
Current high-throughput DNA sequencing methods suffer from several limitations. Many methods require multiple fluid handling steps, fixing of molecules on beads or a 2D surface, and provide very short read-lengths. The NIH inventors offer a DNA or RNA sequencing device that drastically simplifies the process by combining all elements for sequence detection in a single molecule, the Medusa™ Sequencer.

The Medusa™ Sequencer utilizes Forster Resonance Energy Transfer (FRET) to read a polynucleotide sequence while synthesizing a complementary strand. The device consists of a DNA (or RNA) polymerase labeled with a FRET donor fluorophore and attached to a set of four flexible arms. The tip of each arm carries a distinct set including one nonhydrolyzable nucleotide and one FRET acceptor fluorophore. While a Medusa™ Sequencer synthesizes a complementary polynucleotide strand, the four different arms continuously "test" the polymerase pocket creating a characteristic FRET signal for the correct nucleotide. The series of FRET signals reveals the unknown polynucleotide sequence.

Applications:
  • High-throughput DNA or RNA sequencing
  • Alternative to microarrays for expression analysis
  • Diagnostics of genetic diseases


Advantages:
  • Single reagent for synthesis and sequencing
  • Eliminates repetitive fluid handling steps
  • Able to count single mRNA or DNA molecules
  • Exceptionally low manufacturing cost
  • Could be injected in living cells to read/count mRNA sequences directly
  • Low error rate per base
  • High speed; one microscope obtains many sequences in parallel
  • Can be 3D-arrayed in a gel for ultra-high density
  • Use with Sequence Walkers for diagnostics (http://alum.mit.edu/www/toms/g863a.html)


Development Status:
Early-stage

Inventors:
Thomas D Schneider (NCI)
IIya G Lyakhov (NCI)
Danielle Needle (NCI)


Patent Status:
HHS, Reference No. E-194-2005/0
US, , Patent No. 7,871,777, Issued 18 Jan 2011
US, Application No. 12/980,802 filed 29 Dec 2010

and related international patent applications

Related Technologies:
US, Patent No. 8,344,121, Issued 01 Jan 2013, Reference No. E-195-2005/0
PCT, Application No. PCT/US00/23736 filed 29 Aug 2000, Reference No. E-033-1999/0
US, Patent No. 6,982,146, Issued 03 Jan 2006, Reference No. E-033-1999/0
US, Application No. 12/886,686 filed 29 Aug 2000, Reference No. E-033-1999/0
US, Application No. 60/749,858 filed 12 Dec 2005, Reference No. E-195-2005/0
US, Application No. 13/732,029 filed 31 Dec 2012, Reference No. E-195-2005/1


Relevant Publication:
  1. The technology is further described at http://alum.mit.edu/www/toms/patent/medusa .


Collaborative Research Opportunity:
The National Cancer Institute, Gene Regulation and Chromosome Biology Laboratory, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate or commercialize the Medusa™ Sequencer. For collaboration opportunities, please contact John Hewes, Ph.D. at hewesj@mail.nih.gov. Click here to view the NCI collaborative opportunity announcement.


For Licensing Information Please Contact:
Cristina Thalhammer-Reyero Ph.D., M.B.A.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325 Room 33,
Rockville, MD 20852
United States
Email: thalhamc@mail.nih.gov
Phone: 301-435-4507
Fax: 301-402-0220


Ref No: 1322

Updated: 08/2012

 

 
 
 
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