By Ben Butkus
Scientists from UK firms LGC and OptiGene and the University of Southampton are collaborating to develop an ultra-rapid molecular testing platform based on isothermal amplification to diagnose sexually transmitted diseases, the organizations said this week.
The two-year project, which is receiving an undisclosed amount of financial support from the UK government-backed Technology Strategy Board, aims to cut the amount of time it takes to diagnose STDs to 15 minutes or less at the point of care, Paul Debenham, director of innovation and development at LGC, told PCR Insider this week. The TSB is supporting the project as part of an initiative called "Fighting Infection Through Detection."
"The big issue that [TSB] sees is that in clinics, the current technology is all send-away," Debenham said.
"You take a sample and run it on one of these high-throughput analyzers, but it is usually in a remote service laboratory somewhere," Debenham added. "Generally the results come back in about three days, and they've found that the return visit to pick up results is patchy. So there is a health management problem here that can be resolved if you can test and treat in a shorter window, while they're in the clinic, in 15 to 20 minutes."
LGC, an international company specializing in analytical, forensic, and diagnostic services, is spearheading the project, nicknamed CLIENT (clinic-based infection examination through nucleic acid technologies), by working with University of Southampton researchers to develop and optimize LGC's HyBeacons probe technology for STD detection.
HyBeacons PCR probes are short, fluorescently labeled DNA sequences designed to detect DNA mutations and SNPs. According to Debenham, the probes' unique characteristic is the placement of the fluorescent reporter within the probe as opposed to on the ends of the probes.
This arrangement makes the probes "exquisitely sensitive to mutations and SNPs," Debenham said. "It's a very sensitive probe technology for exact matching versus any degree of mismatching. And it works very well in the homogeneous format … so they can be inert through the amplification process, and then you can diagnose whether an SNP or whatever is present just by annealing curve or melt curve analysis."
Specifically, LGC will work with Tom Brown, a professor of natural and environmental sciences at the university, to develop new fluorophores with higher signal-to-noise ratios to up the sensitivity and speed of the HyBeacons probes.
In addition, LGC will work with Ian Clarke, a professor of molecular microbiology; and John Holloway, a professor of medicine, to discover "novel and universally conserved sequences from sexually transmitted bacteria" and to design POC testing kits that will allow direct testing from urine samples without nucleic acid purification.
The researchers have not disclosed which STDs they will target first with their diagnostic tests; however, Clarke is affiliated with a highly regarded chlamydia research group that also works closely with the UK's Health Protection Agency.
Meantime, OptiGene, a UK-based developer of optical analysis instruments, will work with LGC to refine and manufacture OptiGene's benchtop nucleic acid amplification platform, called Genie II. Developed and optimized to work with loop-mediated isothermal amplification, the instrument can be adapted to several types of chemistries requiring temperature control up to 100°C along with fluorescence or luminescence optical detection, according to OptiGene.
Debenham said that LGC and OptiGene had previously worked together under an EU-funded program called the European Pharmacogenetics of Anticoagulant Therapy to investigate the various genetic and environmental factors that affect patient response to warfarin therapy.
OptiGene developed its instrumentation platform for use in that project, Debenham said, "but in that case it was doing PCR" with LGC's HyBeacons probes. However, "in this new project we'll be doing an isothermal methodology, but we haven't decided which yet," Debenham said. "Isothermal is tremendously simple, since it's just a single temperature. And there are definitely some methods out there in the literature, so we're going to explore which ones work most efficiently with the system."
Debenham added that as the group identifies suitable isothermal amplification chemistries, "in some cases they may be freely accessible ... but for others we may be approaching the people that own the IP, and if they're not prepared to license it, then obviously we won't use that technology," Debenham said. "So it will be looking for the combination of the right speed, the ability to work with direct sampling … and obviously accessible with a sensible licensing solution. We're not going to invent a new isothermal amplification method."
Debenham declined to disclose the exact amount of funding being provided by TSB, but said that the project will be funded to about 60 percent of its budget. Overall, TSB's "Fighting Infection Through Detection" program is set to invest more than £12 million (about $18.7 million) in a range of research and development projects to detect infectious agents and test new POC devices.
As far as commercialization rights go, LGC, OptiGene, and the University of Southampton have "an umbrella agreement" in place that will outline who owns any potential IP created as part of the project and how it will be commercialized.
"In general terms, the probe chemistry, or any evolution of our HyBeacon probes – we'll be taking that forward; and the instrument is obviously developed by OptiGene, so they'll be taking that forward," Debenham said.
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