The idea that the human immunodeficiency virus (HIV), a global scourge since the 1980s, could play a role in curing other diseases seems fanciful, a kind of irony that crops up only in science fiction novels. And yet it’s true. A defanged version of HIV that has been modified by scientists to remove the viral components responsible for causing disease and now functions to deliver potentially therapeutic genes into cells is a key component in the work of bluebird bio, one of the World Economic Forum’s 2014 Technology Pioneers.
The company is developing a gene therapy platform to tackle diseases such as adrenoleukodystrophy (ALD), beta thalassemia and sickle cell disease. All are monogenic diseases, which means that they are caused by a problem with a single gene. According to the World Health Organization, diseases of this kind affect millions of people worldwide.
Gene therapy offers the possibility of treating these diseases by adding a functional gene to supersede the malfunctioning one in the patient. Some forms of gene therapy require regular treatment, often over years; but the platform bluebird bio has developed has the potential to be successful with just one treatment and can, according to President and Chief Executive Officer Nick Leschly, “dramatically transform, if not fix the disease.”
The reason that it is possible is that bluebird’s gene therapy uses a lentivirus – a modified HIV, as it happens – which is capable of integrating a functional gene into a patient’s DNA and making a long-term change to the target cells.
“We take the HIV virus and we strip it of all of its virulent components – including its ability to self-replicate,” said Leschly. “That virus is one of the most studied viruses in the world. And you take out those components and all it’s left with is an ability to get into a cell, insert a single copy of a gene, one time. That’s it. And the virus goes away. So we take HIV and we turn it into something good. So we take advantage of its millions of years of honing that skill to hopefully transform a number of diseases.”
Leschly explained how the process works in the case of an ALD patient: “We take out the young boy’s blood cells and outside the body – ex-vivo – we apply the virus. It enters the cell and inserts a therapeutics gene into the cells, in this case they’re specifically CD34 positive blood stem cells or lineages thereof, and then we wash away all the virus so the only thing that goes back into the young boy is what we call the gene-modified cells.
“They go to the bone marrow, they reconstitute the bone marrow and now the difference is the bone marrow has cells with functioning copies of the gene that it did not have before. We’re not a cut and paste. We don’t take out the old one and put in a new one. We just insert functioning copies of the defective gene.”
There is still a lot of work to be done. The technology that bluebird bio uses has been in development for two decades, with considerable strides taken over the last few years. However, progress in medical research of this complexity is slow. Leschly says that bluebird has strong proof of concept that the treatment can be effective for ALD and beta thalassemia and now the work is focused on demonstrating that it is scalable.
Meanwhile, bluebird has plans to expand the treatment to other diseases, including certain cancers. Cancer treatment could be accomplished by modifying T-cells, the white blood cells that form part of the immune system, targeting infections and abnormalities. According to Leschly, “What we were able to do is take the T-cells out of a patient, isolate them and then engineer function into these cells. This is a really hot area of science, it’s called chimeric antigen receptor T-cells. This just means you’re targeting a T-cell to a tumour and then, once it finds a tumour, you’ve rigged it such that it has a self-destruct mechanism right there on the tumour.”
“This now has significant clinical data in the academic setting, so we’re going after blood cancers, but over time we could also go after auto-immune [diseases],” he added.
Author: Shane Richmond writes about technology for the World Economic Forum and is the author of Computerised You: How wearable technology will turn us into computers.
Image: Analysis tubes are seen in a cancer research institute in Sutton REUTERS/Stefan Wermuth.