How Gene Editing Is Curing Disease

this video was made possible by curiositystream sign up today at curiositystream.com real science for just 14.79 and get access to both curiosity stream and nebula for a year sickle cell disease is a cruel genetic disorder that produces a defective form of hemoglobin the protein needed by red blood cells to carry oxygen and deliver it to the body the defective hemoglobin deforms red blood cells into irregular sickle-shaped forms these cells often block the bloodstream causing organ damage and sometimes extreme bouts of pain for one sickle cell patient victoria gray the disease has been crippling for her entire life much of her life has been punctuated by trips to the emergency room due to the pain with life and career ambitions interrupted or put on hold the sickle shaped cells have damaged her heart and many patients with sickle cell don't live beyond middle age strokes or heart attacks are a constant threat around a hundred thousand people in the u.s live with this disease it is the most common inherited blood disorder and affects millions around the world and it is notoriously hard to treat some patients can get help from drugs and others sometimes undergo risky bone marrow transplants but for many these treatments are not enough to get rid of the constant burden of the disease so when victoria gray was exploring the possibility of getting a bone marrow transplant her doctors instead suggested something different in fact something profoundly different to try to treat her disease she jumped up the chance and would become the first patient in the u.s with a genetic disease to get treated with a revolutionary gene editing technique using crispr and now one year later it seems to be working better than any doctor could have guessed the billions of genetically modified cells doctors infused into her body appear to be alleviating virtually all the complications of her disorder so what happened inside victoria gray's body that has left her almost completely free of the symptoms of her disease is the promise of crispr as a medical revolution starting to become realized to understand how crispr is used today let's go back to the beginning of its story when crispr was first discovered in 1987 the researchers didn't really even understand what it is that they had found while investigating a particular gene in e coli they noticed an interesting pattern in the dna surrounding it five identical sequences each composed of 29 bases these repeat sequences were separated from each other by 32 base blocks of dna called spacers which each had a unique sequence the scientists wrote the biological significance of these sequences is not known over the next decade these repeating patterns were found in many different microbes eventually these patterns were given a name clustered regularly interspaced short palindromic repeats crispr for short but scientists still didn't know what they were for but certain observations about them started emerging they were always next to specific enzyme-producing genes labeled as crispr-associated genes or cast genes cast genes encode enzymes that can cut dna but at the time no one knew why they did so or why they were always next to the crispr sequence soon scientists noticed something else about these dna sequences that the crispr spacers the variable sequences in between the repeating sequences looked a lot like viral dna and with this revelation the purpose of the crispr sequences started to become clear that these repeating patterns are a weapon that the bacteria were using against viruses when a virus infects a bacteria it injects its genome into the cell if it is a previously unseen virus a new spacer is derived from the virus's genome and is incorporated into the crispr sequence the spacers are essentially a history of old infections so the bacteria won't be infected again the crispr sequence is then transcribed creating short crispr rna molecules and those repeating palindromic sequences their palindromic nature means that these sequences in the crispr rna can fold in on themselves creating a hairpin structure the crisper guide rna then binds with the matching viral dna the cast enzyme then cuts and destroys the invading viral genome with the hairpin structure helping the cast enzyme to cut exactly where it's supposed to and with a broken genome the virus can no longer replicate itself and the infection comes to a halt when scientists realize that these microbes are effectively programming their enzymes to seek and destroy specific sequences of dna the significance of the discovery started to sink in this could be used as a tool in the past researchers had been able to use restriction enzymes to cut up dna but this did so in an indiscriminate way the crisper cast system instead could make precise cuts giving rise to a whole new area of science what we now know as gene editing crispr technology allows genetic material to be added removed or altered at particular locations in the genome much like hitting ctrl f on your keyboard finding a word in your document and deleting changing or replacing it in order to harness the power of crispr in the lab scientists first design and synthesize short guide rna molecules that match the sequence of a gene they want to edit usually about 20 base pairs long then like in the targeting step of the bacterial system this guide rna shuttles the gas enzyme usually the cas9 enzyme to the intended dna target the cas9 enzyme then makes a cut across both strands of the dna at this stage the cell recognizes that the dna is damaged and tries to repair it scientists can use the cell's own dna repair machinery to add or delete pieces of genetic material or to make changes to the dna by replacing an existing segment with a customized dna sequence and this brings us to victoria gray and her sickle cell disease treatment while sickle cell is indeed a genetic disorder her treatment did not involve going in and deleting or changing the genes that lead to the disease instead scientists found a way to almost completely alleviate the symptoms the treatment called ctx001 tackles the disease by boosting the production of fetal hemoglobin hbf a type of hemoglobin that is present at birth but then stops being produced the idea is that restoring the production of fetal hemoglobin can compensate for the defective hemoglobin produced by sickle cell patients to do this doctors first harvest stem cells from the patient's bone marrow then the crispr cast 9 components are delivered to the cells where they then create a deletion in the gene bcl-11a which encodes a transcription factor that normally represses fetal hemoglobin synthesis this breaks the gene and allows the cells to resume making the protein billions of these modified stem cells are then re-infused into the body they won't replace all of the existing stem cells but if enough of them successfully implant and start producing the needed protein then the treatment will be effective doctors hoped after the treatment that 20 of the hemoglobin in victoria gray's body would be fetal hemoglobin but the results have far exceeded expectations one year after the treatment about 46 of her hemoglobin is now fetal hemoglobin additionally 81 of her bone marrow cells now contain the genetic modification needed to produce the fetal hemoglobin protein indicating the edited cells have continued to survive in her body for an extended period gray's life before the procedure was a constant cycle of dozens of blood transfusions and hospitalizations every year and now after the experimental procedure those numbers have been brought to zero she hasn't had any pain attacks emergency room visits or needed any blood transfusions since the procedure and while gray was the first patient to receive this experimental treatment she was not the only one patients with beta thalassemia have also received ctx001 to restore fetal hemoglobin production their blood disorder causes them to not produce enough normal hemoglobin but gene therapy in several of these patients have left them no longer needing blood transfusions for months now so is this a cure for these blood disorders not exactly but gene therapy like this can potentially prevent many if not all of these diseases complications and the change to these particular patients lives can't be overstated however the treatment is not without its downsides just like for a typical bone marrow transplant recipients of the ctx001 treatment have to undergo chemotherapy to eliminate their own bone marrow to create space for the injection of modified stem cells and just like the chemo for cancer this comes with grueling side effects fatigue nausea mouth sores loss of appetite hair loss it is not trivial gene therapy like this is not the same as taking a pill or a drug it's more like getting an organ transplant and much like cancer treatment it will not come cheap and even though the results from these studies have been extraordinarily promising there are many questions that are still to be answered will the treatment keep working for months or years to come will it help these patients live longer is it safe in the long term and will there be any unintended side effects while these questions do remain it is impossible not to feel optimistic when hearing about these extremely positive results and these blood disorders are just one of many things that crispr has begun to tackle scientists have started researching crispr to reverse genetic blindness muscular dystrophy cystic fibrosis and even cancer and even though gene therapy treatment is expensive crispr technology is in general cheap to test in the past it might have cost thousands of dollars and weeks or months of fiddling to alter a gene using old school knockout techniques now it costs in the hundreds of dollars and takes just a few hours there is still much much research to be done and scientists are just scratching the surface of what is possible with this technology we can't yet know the exact effect that crispr will have in our futures but it is going to be huge science has progressed towards a much better understanding of genetics but there is still so much we don't know in many ways our genes are a book that can be read to determine our destinies leading to our good health or sometimes our unfortunate illnesses but scientists are becoming more aware that dna doesn't explain everything and that our environments and our experiences play a greater role in how our genes are expressed than previously understood if you want to learn more about how environmental factors can determine which genes are turned on and off then you should watch our genes under influence on curiosity stream it's a 50-minute in-depth film that explores how identical twins with the same dna can be physically different how generations of plants can be physically modified without changing the dna sequence at all and how epigenetics shapes our 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Channel: Real Science

Views: 112,073

Rating: 4.9660373 out of 5

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Id: ezfwqmKC9Uc

Length: 13min 32sec (812 seconds)

Published: Sat Aug 22 2020

Reddit Comments

[u/IcanSew831]

I’m so glad this is working.