Breakthrough: super fast DNA tests

A rapid bedside genetic test can screen newborn babies for a genetic variant which makes them susceptible to hearing loss due to antibiotics. The test could save 14,000 neonates a year from deafness. David Budd, chief executive of Genedrive which developed the test, explains the mechanics behind it.

Forward: features are independent pieces written for Mewburn Ellis discussing and celebrating the best of innovation and exploration from the scientific and entrepreneurial worlds.

Q: David, what is your test?

We operate in the world of pharmacogenomics. This is the study of how someone's genetics interacts with pharmaceuticals. It's a field that's been around for more than 30 years, mostly in cancer care, but is now making progress in other disease areas.

Our company created a system which tests for the genetic variant m.1555A>G in 26 minutes using a simple cheek swab. New born babies suspected of sepsis are usually given antibiotics, typically gentamicin. For babies with this variant the sepsis is cured but they will suffer serious life long hearing damage. Our test means we can rapidly identify the variant and the baby can be given alternative antibiotics, thus saving their hearing.

Q: How are you able to deliver the results so fast?

There are four things that drive the speed. The first is the design of our instrument. We use a very small amount of the patient's sample. In the molecular world, the larger the sample volume you take the longer the test can take. We are only looking at 5 to 10 microlitres of patient sample. Second, is the molecular technology around amplification. A premise of molecular diagnostics is that your genes are full of information, but they are so tiny that you can't really see them. So the first phase is to amplify the information. PCR is the most famous method, which we've all heard of because of Covid. We are using a faster technology called Loop-Mediated Isothermal Amplification or LAMP. It's not as sensitive as PCR, but appropriate for our needs in this application and much faster to process. The third thing is we have developed a workflow that doesn't require isolation of the patent's genetic material from their cells. Normally in molecular diagnostics you have blood or nasal fluid and you need to clean it up, to remove anything that potentially interferes. We are able to work with a dirty sample, for want of a better term. And the last thing is the focus of our search. We are looking for what are called SNPs (“snips”), which stands for single nucleotide polymorphism. We are not sequencing the entire genome, which is overkill. Put these together and you have a test which can deliver genetic results well inside the hour needed to help the baby.

Q: How many babies do you expect to save?

The m.1555A>G variant is present in between one in four to five hundred babies. In terms of babies in the UK we can help it is around 200 to 250 a year, or 14,000 a year globally. When you ask someone who is deaf and they say they were born deaf, well, there's a good chance they weren't but were put on antibiotics with this variant and lost their hearing. So we are making a real difference.

Q: What other applications are there for this style of super-fast testing?

It's useful in any clinical situation where a genetic disposition may interact with pharmaceuticals and you need a rapid answer without going to the expense of a time-consuming full genetic test, or you haven’t got the time to send the sample away to a genetic testing laboratory. Stroke patients are another good example. A stroke victim will be taken to hospital by ambulance and often put on anti-platelet therapy to stop their blood clotting again. Most people get the drug Clopidogrel. It is metabolised in the liver. Not everyone is a good metaboliser for genetic reasons. The pathway is called CYP2C19. So you could have a stroke, receive Clopidogrel in A&E and be a non-responder. A quick analysis of a person's CYP2C19 gene would tell you if they are suitable for this treatment. There are other non-urgent applications too, such as anti-depressants being prescribed, and you simply want to know whether there are any adverse genetic complications in associated with a specific drug and want a quick answer.

Q: How developed is this technology?

Our system is being tested in two NHS hospitals in the North-West of England. So far there are just a handful of applications of this type of testing in pharmacogenomics. We see the payback as tremendous. Of course, the economics are a little more complicated, as the immediate expense is borne by the hospital, and the savings are a lifetime of treatment at an audiology department. Our hope is to transform the lives of hundreds of babies a year in the UK alone who will grow with perfect hearing. We are convinced this approach has a very bright future.


The field of rapid sequencing and bioanalytics is maturing

Eliot Ward, Partner and Patent Attorney at Mewburn Ellis comments:

As a father of a child who was given gentamicin at birth, I vividly remember the anxiety of knowing that there was a risk of severely damaging his hearing. This invention cannot come soon enough for parents and babies alike. It also shows that the field of rapid sequencing and bioanalytics is maturing. IP protection will continue to play a vital role in supporting its development. As in any maturing field, a careful analysis of new innovations as they arise will be key to forming an effective patent strategy.


Written by Charles Orton-Jones