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TriLink Biotech Wins $100K NIH Grant to Develop 'Hot-Start' Ligase Chain Reaction


TriLink Biotechnologies said today that it has recently been awarded a Phase I SBIR grant worth approximately $100,000 by the National Institutes of Health to develop a hot-start approach for the ligase chain reaction method.

Under the six-month grant, administered by the National Institute of General Medical Sciences, TriLink will incorporate chemically modified ligation components, including oligonucleotide probes and cofactors, containing thermally labile protecting groups for heat-triggered LCR.

TriLink hopes that these modifications will provide the same benefit as hot-start approaches for PCR; namely, a substantial improvement in specificity and performance compared to conventional LCR, according to the grant's abstract.

LCR, developed in the early 1990s in the laboratory of Francis Barany at Weill Cornell Medical College, is a DNA amplification technique that can be used in conjunction with or as an alternative to PCR due to its equal ability to support exponential signal amplification.

According to TriLink, the method has been used in molecular biology and diagnostic applications, especially for nucleotide sequence and single nucleotide polymorphism detection.

However, performance problems and non-specificity issues, including the accumulation of false-positive signals, have often hampered the use of the technique for these types of applications.

"It is not widespread now at all," Alexandre Lebedev, a senior principal scientist at TriLink and principal investigator on the NIGMS grant, told PCR Insider. "We are looking to improve this technology so it will be at the same level as PCR or other commonly used diagnostic techniques … in terms of sensitivity, specificity, and throughput."

Lebedev explained that if its performance issues can be resolved, LCR has the potential to be more useful and less expensive than PCR and other techniques, particularly in multiplex applications.

"I believe LCR can be very important in multiplex detection," Lebedev said.

The grant will be funded through July, and is the fifth Phase I SBIR awarded to TriLink, the company said.

TriLink, based in San Diego, manufactures custom oligonucleotides, modified nucleoside triphosphates, and CleanAmp PCR products for the diagnostic and OEM markets. In addition, the company offers custom chemistry, contract research services, and cGMP production facilities.

"Moving into LCR is a natural progression for TriLink," President and CEO Richard Hogrefe said in a statement. Hogrefe added that TriLink "gained a unique perspective on the limitations of LCR, and the technical knowledge to solve them" while developing its CleanAmp PCR products and through its ongoing ligation work.