Intracellular RNA Sequencer

The National Cancer Institute, Center for Cancer Research Nanobiology Program seeks a research and development partner to develop a single molecule sequencing device.

The Medusa(TM) Sequencer consists of a DNA or RNA polymerase functionalized at each end with a pair of flexible, long chain groups. At the end of each group is a nonhydrolyzable nucleotide and a spectrally distinct Forster Resonance Energy Transfer (FRET) acceptor fluorophore. A FRET donor fluorophore is attached to the polymerase and can excite the acceptor fluorophores. A Medusa(TM) Sequencer binds to a DNA primer that has been hybridized to the DNA or RNA to be sequenced. As the four nucleotide tips "test" the polymerase pocket, the arm that has the nucleotide tip complementary to the unknown base of the sequence will dwell longer than the other three that are not complementary. The energy transfer between fluorophores produces a characteristic spectrum that identifies the bound base. Free hydrolyzable dNTPs or NTPs allow the Medusa(TM) Sequencer to step forward. The series of FRET signals reveals the unknown nucleotide sequence.  The technology is further described at http://www.ccrnp.ncifcrf.gov/~toms/patent/medusa/

Main Advantages of Technology/Invention:

• Accurate counting of individual mRNAs or DNAs
• Low error rate per base, which can be improved by modifying the polymerase
• Speed: a single microscope can be used to obtain many sequences in parallel

Further R&D Required:
Prototype development

Patent Status:
PCT application filed 12 Dec 2006.

Contact Information:
John D. Hewes, Ph.D., Technology Transfer Specialist
Phone: 301 435 3121
E mail address: hewesj@mail.nih.gov
 

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