DNA Sequencing Technologies - Isis Project No 1451

Two technologies for DNA Sequencing: Ligation Method and Parallel Sequencing.

Ligation Method: Cost effective parallel DNA sequencing method, particularly suitable for microarrays.

Market demand

The demand for lowering the cost of sequencing DNA is expected to strengthen in the near future, especially as information about human genomes leads to more personalised medicine.

There is already a major drive underway to develop faster and lower-cost alternative methods.

Ligation-based technology

Oxford University researchers have patented a ligation based sequencing technology that can be implemented at bulk or single molecule level.

The method is also particularly appropriate for implementation on microarrays.

Oxford method advantages

• Requires short development time

• Cost effective compared to existing methods

• High accuracy of ligation reactions

• Microarray platform application option

• Uses off-the-shelf reagents

• No reliance on new chemistries or platforms

• Easy software for base-calling

Technology maturity

Proof of principle of the patented method is published in Nucleic Acids Research:
Sequencing by Cyclic Ligation and Cleavage (CycLiC) directly on a microarray captured template. Mir KU, Qi H, Salata O, Scozzafava G., Nucleic Acids Res. 2009 Jan;37(1):e5

Patent status

This method has been granted a European patent (EP1689881) and is pending on another (WO2005/040425). Isis is looking for potential licensees and collaborators to commercialise this technology. Please contact the Technology Transfer Manager by using the link below.

------------------------------------------------------------------

Parallel Sequencing: A single molecule, real-time sequencing technology that avoids consecutive additions of reagents and extensive washing cycles.

DNA sequencing

The last few years has seen the emergence of second generation sequencing technologies which have hugely reduced the cost of sequencing genomes. However, the cost has not reached a level where human genome sequencing can play a part in routine health management. This is partly because current human-genome scale sequencing technologies are based on cyclical additions of reagents in excess, which is costly. Oxford researchers have now developed a single molecule, real-time sequencing methodology with several benefits.

The Oxford invention

• Involves a homogeneous reaction.
• Does not require consecutive additions of reagents or extensive washing regimes.
• Detects the incorporation of fluorescently labelled nucleotides in real time as template-directed DNA synthesis proceeds.
• Is a unique method in that it uses dyes that continually intercalate into the growing duplex as FRET donors to base-specific acceptor dyes.

Competitive advantages

• Background signal in solution is circumvented by the use of a FRET mechanism.
• Avoids deletions in the sequence from one to tens of bases in length read that are caused by the blinking of individual FRET donors.
• Does not rely on a specific polymerase enzyme and may be compatible with proprietary polymerases.
• Removes the need to conjugate a FRET label to the DNA polymerase.
• Does not require a nano-engineered surface structure, which can increase cost and limit throughput.
• Provides methods for relatively long sequence reads and information about the genomic location of the sequence.

Technology maturity

The technology is at an early stage and proof of principle has been demonstrated for various aspects of it. Isis is looking for potential licensees and collaborators for further development of the invention.

Patent status

This technology has two patents pending (EP2270206 and WO2005/040425). Isis would like to speak to companies interested in commercialising this technology. Please contact the Technology Transfer Manager by using the link below.

Request Further Information: DNA Sequencing: Ligation Method - 1451