Gene therapy comes of age

Oxford BioMedica may have a cure for leukaemia. Its share price has soared since the last week of June. Its treatment uses a modified version of the HIV virus to insert a cancer-killing gene into patients’ cells. This is a stunning example of how gene therapy will revolutionise medicine in the future. And there are many other players working in the incredible field of gene therapy. More widespread genome sequencing opens up the possibility of personalised treatments. The news coming out of the laboratories is encouraging – not least for investors.

In the city of dreaming spires…

John Dawson, CEO of Oxford BioMedica (LON:OXB) has been preparing the firm’s Oxford laboratories for some important visitors. Any day now, a team of white-coated technicians from America’s Food and Drug Administration (FDA) will call by to inspect. If they like what they see, then OXB’s new drug – CTLO19 – could be licensed for use in the USA by as early in October. A European Medicines Agency (EMA) filing is likely to follow soon after.

This new drug uses a stripped-down version of the HIV virus to reprogram a cancer-sufferer’s immune system to kill cancer cells. In a treatment that OXB devised in partnership with Swiss pharma giant Novartis AG (VTX:NOVN) and the University of Pennsylvania, the drug can be administered by one simple injection.


Analysts reckon that the drug could generate a considerable income stream. Each treatment could cost up to US$400,000 per patient in the USA, on which OXB would receive a royalty of about three percent. That could mean additional future revenues of an estimated US$127 million per year for a company that turned over just US$40 million last year. Consequently, OXB’s share price has gone from 5.56 pence on 26 June to 9.25 pence this morning, having hit 10.25 pence on Wednesday.

Not before time, some investors might cry. OXB floated on the AIM more than 20 years ago in December 1996 with an initial market capitalisation of £50 million. That figure is up to £285 million today. OXB has been working with some big pharma players like Glaxo SmithKline (LON:GSK) and Sanofi (EPA:SAN) as well as other niche players like Orchard Therapeutics (a private UK firm also active in gene therapy); but this is its first major breakthrough.

How it works

Leukaemia, of which there are numerous kinds, is a group of blood cancers which originate in young white blood cells (lymphocytes) in the bone marrow. It accounts for about a quarter of all cancers diagnosed in children under 15, and affected 760 British children in 2014.

OXB’s new treatment works by removing T-cells – a type of lymphocyte which plays a key role in cell immunity – from the patient and then “reprogramming” them genetically in a lab. The genetically modified T-cells are then injected back into the patient’s bloodstream where they multiply and attack cancer cells. OXB has found a way to strip out the capability of the HIV virus to reduce immunity yet still retain its ability to impart specific genetic material (DNA) into host cells.

In the first global trial of the treatment, carried out on 63 youngsters in the USA, 52 (83 percent) experienced complete remission, according to Novartis. That is remarkable.

In the first global trial of the treatment, carried out on 63 youngsters in the USA, 52 (83 percent) experienced complete remission, according to Novartis. That is remarkable.

Genetics for dummies

For non-medics (like me) let’s just make sure we are all on the same page. Genes are particles in cells, contained in chromosomes, and made up of long helical strands of DNA (deoxyribonucleic acid) molecules. DNA contains all the instructions for building proteins which in turn control the structure and function of all the cells that make up your body. The entire sequence of genes in each and every cell in your body is called your genome.

We are often told to think of our genes as an instruction manual for cell growth and function. Abnormalities in the DNA are said to be like typographical errors. They may provide the wrong instructions, leading to faulty cell growth or function. In any one person, if there is an error in a gene, that same mistake will appear in all the cells that contain that gene. This is like having an instruction manual in which all the copies have the same typographical error. Gene editing may be seen as a way of correcting those errors.


The problem is that this metaphor of the “typographical error” assumes that there is only one correct spelling in nature; whereas nature throws up multiple and various ways of solving the same problem, no single one of which is “correct”. (Blue eyes and brown eyes are both equally “correct”). We can all agree however, that inherited conditions like cystic fibrosis are inimical to good health and that we would be better off without them.

A call to arms

On 04 July Chief Medical Officer for England, Dame Sally Davies, published a report, Generation Genome, in which she called upon the NHS to widen its use of gene therapy. Dame Sally, who is a haematologist by background, is managing a pilot project known as the 100,000 Genomes Project. So far, about 70,000 NHS patients with rare diseases have had their genomes sequenced. In future, specific treatments could be tailored according to a patient’s individual genome.

This approach has already yielded results. A 13-month-old baby named Jessica was subject to a condition which manifested itself in violent seizures. Her entire genetic code (genome) was mapped and then compared with a “standard” human genome. Some 6.5 million genetic variations were identified, of which 700,000 were considered “rare” and 3,000 critical. At this point scientists compared Jessica’s genome with that of her parents, who did not have the disease. They had the same 3,000 genetic variations – bar 67.

In future, specific treatments could be tailored according to a patient’s individual genome.

When these 67 were cross-tabulated against a database of symptoms, just one match was found: Gene SLC2A1 – which is a glucose transporter – it creates a protein that conveys sugar to the brain. It turned out that Baby Jessica only had one copy of this gene, when most people have two. Her body was not producing enough glucose to feed her brain. In this particular case, genomics provided a diagnosis of a condition which could be addressed with a low-tech solution: Baby Jessica was given glucose supplements and is thriving.

Dame Sally advocates that all cancer patients should get their genome sequenced. I have no doubt that, eventually, we shall all have our entire genome sequence encoded on our credit card-sized identity cards – or, even more likely, on a microchip implanted in our necks. Robots will scan these to devise the most appropriate treatment for our particular condition, given our genetics, and will offer us a menu of treatment options. But don’t expect this to happen quickly in our slow-moving NHS.

Fancy a burger grown in a lab?

Gene therapy goes beyond medicine. One fascinating application lies in food production.

A number of start-ups are working on growing cultured meat in labs. This is seen as a way to reduce greenhouse gas emissions which drive global warming, and also to address animal welfare concerns. I know that some vegetarians avoid meat for health reasons but most also believe that slaughtering animals for food is cruel. Moreover, we are running out of land for pasture and the oceans’ stocks of fish are under pressure in a world of getting on for eight billion people.

Memphis Meats of California has grown both “chicken” and “pork” meatballs in a lab derived from animal stem cells[i]. (I’m not sure if veggies will approve.) Apparently, the product is edible – the problem is the economics. Currently, a pound of lab-reared beef would cost US$18,000. The company claims that the cost will become economic as production technology improves and as it achieves economies of scale.


Another San Francisco start-up is focussing on fish-based foods. They point out that most fisheries are exploited to full capacity and many are in a state of collapse: therefore production of synthetic fish products is a necessity. As well as economics, there will be a problem of perception before such food products can be successfully commercialised. Not to mention taste.

In the UK each citizen eats, on average, 80 kilograms of meat per year. That figure is quite stable; but globally, meat consumption is on the rise as living standards improve in developing countries, not least in Africa. On current projections, global meat consumption will nearly double by 2050.

I am cheered that astronauts heading to Mars in the late 2030s (no doubt members of the MI team amongst them) will be able to tuck into a decent Sunday (lab) roast lunch with all the trimmings.

The Great British Gene-Bake

The really encouraging thing is that British companies and scientific institutions are in the vanguard of this astonishing new field. It was in Cambridge, UK, that the DNA helix was first described by Francis Crick and James D Watson in 1953. Nearly 65 years later, Britain is leading the world in gene therapy.

Leading British genomics companies include Oxford Nanopore Technologies which has developed hand-held DNA readers which are already being used on the International Space Station (ISS). Eagle Genomics and Congenica are working on genome sequencing technologies which will bring the cost of sequencing an individual’s genome to about £680 a pop, according to one newspaper. And yet, I have received numerous emails from Ancestry.co.uk offering me the chance to unlock the secrets of my heritage for just £79! That is less than the attributed cost of one average visit to an NHS doctor.

One issue holding back the British biotech sector is the reluctance of the NHS to outsource genomics to commercial third parties. This is something that needs to be addressed.

Once again, the real competition is not in Europe but in America where there are larger, more mature rivals such as Foundation Medicine Inc. (NASDAQ:FMI), Quest Diagnostics Inc. (NYSE:DGX), Labforce and Grail.

One issue holding back the British biotech sector is the reluctance of the NHS to outsource genomics to commercial third parties. This is something that needs to be addressed.

Moral implications

Gene therapy and gene editing technology will have the power to modify an individual’s genome and those of their progeny (the modification will be passed on). In this way certain types of hereditary diseases such as Duchenne muscular dystrophy might be eradicated forever.

But, as ever, there is a catch. We know that some genes are multi-functional and may have both deleterious and beneficial consequences. For example, scientists know that there are two genes which seem to have an important role in breast cancer which they have named BRCA1 and BRCA2. About 5 percent to 10 percent of breast cancers are thought to be hereditary – caused by abnormal genes passed from mother to daughter.

But you couldn’t just splice these genes out without consequences because we know that they have a role in repairing damaged cells. Mutations in pieces of chromosomes – called SNPs (single nucleotide polymorphisms) – may be linked to higher breast cancer risk in women with an abnormal BRCA1 gene, as well as those women who have not inherited an abnormal breast cancer gene[ii]. The way forward is therefore uncertain.


And it’s not just humans who are in the frame. Every living organism on Earth (and potentially beyond), animal or vegetable, has a genome. So genetic manipulation has almost limitless possibilities. Scientists already have the capability to bring woolly mammoths back to life – by inserting their DNA into elephants. By extension, Jurassic Park cannot be far away.

This opens up a moral quagmire – scientists playing God. Just how far we want to go down the road of genetic manipulation will raise nagging philosophical questions. Do we wish to create the perfect human?

And what would Islamic State do with this technology? I suppose they would attempt to eliminate the gay gene (if there is one – there are probably many). That way, humanity would be deprived of not just fine interior designers and ballet dancers, but some of its most illustrious soldiers, writers, athletes, artists and scientists. The downside of this god-like power could be much worse than its upside.

But for now, the prospects are hopeful. My own father died of leukaemia, so I know something about the endless blood transfusions and hospital admissions associated with this condition. And how much worse must it be for the parents of young children who succumb to this awful scourge. If leukaemia could be beaten, I’d call that progress.

[i] See: http://www.bbc.co.uk/news/av/technology-40496863/lab-grown-meat-the-future-of-food

[ii] See: http://www.breastcancer.org/risk/factors/genetics