CRISPR Gene Drive (Complete guide 2019)

a gene drive to eradicate malaria is a hot topic gene drives could once and for all wipe out malaria saving the lives around half a million people per year and this might not be far off very recently researchers from the Imperial College in the UK used a gene drive in the lab to kill off every single malaria carrying an awful East gamba mosquito from a population of 600 a gene drive is a technology with which we are able to alter an entire species from within genetically modified animals we’ve made in the past are usually worse off in the wild and the mutations don’t get passed down the generations but a gene drive changes this it changes the mutation we make into a genetic invader at least in theory no wonder it has caused tons of excitement and also lots of worry thankfully scientists researching the gene drive have called for the science of gene drives to be very open here I take a look at the problems the technology faces how they can be overcome and something that is not as much talked about gene drive applications for environmental conservation gene drives can be used to spread a sterilizing mutation throughout a species the gene drive mosquitoes created by researchers from Imperial College contain a genetic modification that either makes them sterile or it makes the mosquitoes spread the gene drive to the next generation eventually bringing the whole population down gene drives occur naturally in many species but have been very difficult for man to engineer but with the new precision gene editing technology CRISPR has nine engineering a drive is now possible let’s take a look Chris Perkis name is as system bacteria used to battle viruses and works by comparing storage strands of viral DNA in the bacteria’s genome with the DNA of viruses invading the bacteria if the CRISPR caste 9 system finds DNA that matches its stored guide virus sequence it cuts the invading DNA precisely at that location stopping the virus in a GU drive we make use of crispers ability to make accurate cuts but to understand a gene drive we need to know how cells repair damage to DNA most sexually reproducing organisms cells have pairs of chromosomes with a variant or a version of a gene on each chromosome if for some reason one of the chromosomes gets cuts the sale often repairs the cuts using the opposite chromosome as a template so minimal information is lost in Ag drive we’ve replaced the original virus guide sequence stored by the bacteria with the sequence of the DNA on the chromosome opposite the gene drive this guides the CRISPR cast 9 to make a cut on the other chromosome sabotaging it and the cell fixes the cut by copying the gene driver to the damaged chromosome a precision cost to the chromosome opposite the gene drive done with the CRISPR caste 9 system makes a gene drive work and now the invading gene drive is on both chromosomes and can spread to all offspring as long as the system works like this no problems arise and the gene drive spreads but resistance against the gene drive can develop in the species the cell doesn’t always fix cuts in DNA by copying the other chromosome it can also just trim away some DNA around the cut and close the gap it’s a bit messy but often gets the job done in this case the gene drive does not spread to the other chromosome and in addition the other chromosome sequence has changed in the repair if it changes too much the CRISPR guide sequence won’t recognize it anymore and the CRISPR Caston I can’t cut it and the gene driver stops working this altered sequence can spread through the population and act as a stopper for the gene drive the spread of this altered sequence is likely if having the gene drive makes the animal worse off and is not favored by natural selection resistance to gene drives has been a problem in lab experiments in the mosquito experiments resistance was overcome by adding the gene drive on top of a vitally important gene that is used to determine the sex of the mosquito when the gene drive works as it should it cuts the other chromosome and copies itself on top of the vital gene breaking it and making the mosquito sterile but when the cell doesn’t fix the COTS by using the other chromosome with the gene drive as a template and just sticks the ends of the broken chromosome together the gene also breaks it can’t tolerate losing DNA and since the gene is so important breaking it also makes the mosquito sterile both methods lead to sterile female mosquitoes the altered sequence formed by sticking the ends of broken chromosome together that might cause resistance doesn’t get passed on to the next generation meanwhile the males do fine with the gene drive in their chromosomes and they spread the drive on to their offspring eventually the gene drive has spread through the whole population without resistance forming and the population crashes more experiments have to be done to test how the drive works in most Kito’s in more natural settings like larger cages since resistance may still arise and the viability of modified mosquitoes might be a problem in larger populations in the wild but this is a step towards a working drive and if we ever get there there is no limitation as to how far it can spread when the goal is to eradicate area carrying mosquitoes this can be a good thing but for applications like conservation this is detrimental controlling invasive species is really difficult a newcomer species has no natural enemies in a new environment like an island and it can rapidly spread causing extinctions of species in the local ecosystem New Zealand is a good example of an island with many invasive species like the common root which arrived with European settlers it has since spread throughout the islands causing destruction to bird and lizard populations combating it is very difficult expensive and causes harm to the environment a gene drive on the other hand would be a relatively cheap solution a small amount of animals would be released in the wild without any poison or traps needed and the invasive population would vanish completely dying a natural death we would not control the living world with steel or poisons but by learning to speak its language combating invasive species is so difficult at present that new technologies are needed a gene drive could be one such technology but there’s a big problem even a small amount of common rats with a population limiting gene drive escaping New Zealand could wipe out every single common rats upon earth a workaround for this could be a daisy try a daisy drive is a gene drive that has a limited lifetime the drive would be made of multiple gene drives linked in a chain where a would cut the DNA for a b and b would cut the DNA for a C and so on the final elements being driven would contain the payload the sterilizing mutation for example none of the drives would spread itself each would depend on the drive up the change to make the cut but there would be nothing driving a meaning that it would get diluted in the gene pool like any normal gene after a has gone B gets diluted next since a doesn’t drive you to jump to the other chromosome and so on the more drives link together the longer the payload would affect the population even if an animal with the Daisy Drive escaped it would not spread the drive for hour before the drive would be diluted in the gene pool other populations would be safe Daisy drives have only been tested with mathematical models and not in any animals Daisy drives for a rat eradication or eradication of any invasive mammal species is still far off we need to get the drive itself working in a novel first mammalian experiments have been done in mice but getting the basic drive to function has proven difficult the gene drive is a fascinating technology with potential for great good but also great harm an accidental release of a drive without restrictions could shift global ecosystems drastically and field testing of a gene Drive should be carefully considered on a case-by-case basis if AG drive were released to the wild a reversal drive should be ready in case anything went wrong it would be released and it’s going sequence would target the first gene driver released removing it from the population thanks for watching make sure to subscribe and share this video personally I’m very excited and a little terrified when it comes to gene drives there is so much potential there if we proceed with caution and research it thoroughly before any applications it can give so much to both humanity and nature around us how do you feel about gene drives for malaria eradication and for conservation I’d like to hear your thoughts in the comments and check out the other videos on this channel see you again you [Music]