Last post, I looked quickly at how genetic treatments worked. It seems that restoring hearing through genetic therapy is still far away. But progress is being made.
From what I gather, there are 3 phases to testing gene therapies. First is in a test tube or lab dish (in vitro), next is in live creatures (in vivo); mice or other animals, and finally humans. I don't believe there are any human trials for hearing and gene therapy underway - at least I haven't found any publications. However there are a lot of animal trials out there.
Some of these use a virus called AAV to transfer genes to the ear. Viruses work by injecting their DNA into our cells. Our cells then make the proteins the virus wants. This video explains more about viruses if you are interested.
AAV is a virus which infects people but doesn't seem to do any damage, and your body doesn't seem to be bothered by it - it doesn't trigger much of an immune response. In fact there is a good chance you have already been infected by it.
AAV only needs some of its own DNA to spread itself. To use it in gene therapy, scientists keep this bit of DNA and replace the rest with whatever they want- such as GJB2, the gene for creating Connexin 26.
Testing this on mice and guinea pigs does lead to the cells creating good Connexin proteins, and restores the ear battery I described in a previous post. But this did not repair their hearing. The problem is is that many Cx26 and Cx30 mutations lead to the death of hair cells in the ear, and these don't grow back in mammals. Hair cells are the cells that detect sound and convert it to a nerve signal. So if you fix the mutation after the hair cells are dead, it's not going to make much difference.
This leads to a problem for human treatments. Most of the time, the hair cells are dead at birth, or soon after. Which would mean trying to carry out treatment when a baby is still in the womb; a lot more risky than treating adults or even children. But there is research being done on how to regenerate hair cells, meaning the treatment could work after birth.
So it looks like we wont be seeing genetic remedies for Connexin mutations any time soon. Perhaps the CRISPR technology I mentioned in my last post will change that - you can already buy CX26 CRISPR bacteria online, so I guess someone is doing research with them.
Finally, here's something not related to hearing but still interesting. Connexin 26 is actually being looked at in gene therapy to fight cancer. Scientists have come up with DNA which will kill a cancer cell. But they have difficulty getting it into them. For some reason, cancer cells don't produce much Connexin protein. Connexins are used to allow stuff to pass between cells, so if they aren't there its harder to get new DNA into the cancer cells. Using AAV, scientists stick in the GJB2 gene alongside the new cancer-killing DNA, and it has shown to be pretty effective in some cases.
However in other cases it has allowed the tumors to spread more quickly - so more research needed! Still, looks promising.
Tuesday, 16 January 2018
Wednesday, 3 January 2018
Genetic Treatments and CRISPR
My son's hearing has effectively been restored through the use of cochlear implants, and with great success so far. However I have often wondered if it would ever be possible to fix the underlying biological problems that cause the hearing loss. There is some research being done to see if gene therapy could be useful for this.
Gene therapy is where you go in and alter the DNA within a cell, to fix whatever ails it. This can either be 'knocking out' or switching off a faulty gene, replacing a gene with a healthy version, or introducing a new gene into the cell. As you can imagine, how this is done is pretty complicated and to date has been very difficult.
First off, it's no use changing the DNA of one cell. If we are trying to repair Connexin genes, you'll need to do it to a good chunk of cells in the ear - i'm guessing millions. And you want it focussed. There's no point in sending new Connexin genes into my shoulders, knees or bladder. You any as well be pissing them away, and you might actually do damage.
So you need a delivery vector. This is usually a modified bacteria or virus, which are very good at spreading themselves around specific parts of the body. But you don't want your immune system attacking the delivery vector, so you need to be careful about what you use. And you don't want the new gene going into the wrong part of your DNA - it might split another gene, causing major problems.
Because of this complexity, there are not many gene therapy treatments out there that are in use. That may be about to change however, due to something called CRISPR. This new technique allows us to neatly cut out bits of DNA we don't want, and replace them with ones we do. I'm not going to go into how it works exactly. I will however link to this snazzy (if somewhat lacking-in-content) video.
One thing I find really fascinating about CRISPR is where it came from. The technique for cutting out specific bits of DNA evolved in bacteria. They used it to defend them against viruses - scientists just had to tweak it a bit.
Viruses don't reproduce by themselves. They get our cells to do it for them. They inject their DNA and it becomes part of that cells chromosome. Our cells own reproduction process then copies it, until the cell is full of virus DNA and literally bursts, releasing more viruses. Bacteria and viruses have been fighting against each other for billions of years (probably), and this evolutionary pressure has given some bacteria a useful tool. They are able to recognise 'foreign' DNA. They then copy it and strap it on to come chemicals. If the chemicals find other DNA that matches, they destroy it.
This was first noticed by yoghurt scientists, trying to see how bacteria used in fermentation defended themselves. Scientists have added to it by getting the chemicals to replace the destroyed DNA with DNA of their choice. I've no idea how.
The explanation above is a massive oversimplification, and as it may be clear I don't fully understand the technique. But there is tonnes of stuff online about it, and it all suggests that this is going to be a revolution for genetic treatments. It has already been used to edit DNA in some animals, and has actually been used to cure a rare genetic liver disease in mice. Some of the scientists behind it were tipped to win a Nobel prize in Chemistry in 2017, but it didn't happen. The law case over patents and who actually developed the technique probably didn't help.
Gene therapy is where you go in and alter the DNA within a cell, to fix whatever ails it. This can either be 'knocking out' or switching off a faulty gene, replacing a gene with a healthy version, or introducing a new gene into the cell. As you can imagine, how this is done is pretty complicated and to date has been very difficult.
First off, it's no use changing the DNA of one cell. If we are trying to repair Connexin genes, you'll need to do it to a good chunk of cells in the ear - i'm guessing millions. And you want it focussed. There's no point in sending new Connexin genes into my shoulders, knees or bladder. You any as well be pissing them away, and you might actually do damage.
So you need a delivery vector. This is usually a modified bacteria or virus, which are very good at spreading themselves around specific parts of the body. But you don't want your immune system attacking the delivery vector, so you need to be careful about what you use. And you don't want the new gene going into the wrong part of your DNA - it might split another gene, causing major problems.
Because of this complexity, there are not many gene therapy treatments out there that are in use. That may be about to change however, due to something called CRISPR. This new technique allows us to neatly cut out bits of DNA we don't want, and replace them with ones we do. I'm not going to go into how it works exactly. I will however link to this snazzy (if somewhat lacking-in-content) video.
One thing I find really fascinating about CRISPR is where it came from. The technique for cutting out specific bits of DNA evolved in bacteria. They used it to defend them against viruses - scientists just had to tweak it a bit.
Viruses don't reproduce by themselves. They get our cells to do it for them. They inject their DNA and it becomes part of that cells chromosome. Our cells own reproduction process then copies it, until the cell is full of virus DNA and literally bursts, releasing more viruses. Bacteria and viruses have been fighting against each other for billions of years (probably), and this evolutionary pressure has given some bacteria a useful tool. They are able to recognise 'foreign' DNA. They then copy it and strap it on to come chemicals. If the chemicals find other DNA that matches, they destroy it.
This was first noticed by yoghurt scientists, trying to see how bacteria used in fermentation defended themselves. Scientists have added to it by getting the chemicals to replace the destroyed DNA with DNA of their choice. I've no idea how.
The explanation above is a massive oversimplification, and as it may be clear I don't fully understand the technique. But there is tonnes of stuff online about it, and it all suggests that this is going to be a revolution for genetic treatments. It has already been used to edit DNA in some animals, and has actually been used to cure a rare genetic liver disease in mice. Some of the scientists behind it were tipped to win a Nobel prize in Chemistry in 2017, but it didn't happen. The law case over patents and who actually developed the technique probably didn't help.
Subscribe to:
Posts (Atom)