Disclaimer: Genetic engineering is a very wide field, there are a lot of different technologies that are being used, but in this post, I only really look at one. If you find yourself interested in this technology I advise researching other types of technologies which are used for genetic engineering.
Introduction
Malaria is one of the deadliest diseases in the world, with an estimated 300-600 million people suffering from it as well as over 1 million deaths a year. Being raised in Nigeria I’m particularly aware of the prevalence of Malaria especially when focusing in on Sub-Saharan Africa, where over 90% of cases occur. With the large amounts of cases that occur every year, the success of treatment and prevention has been limited. Genetic engineering is relatively new and may perhaps be the most effective form of treatment/prevention to date. Genetic engineering can simply be described as the process of altering the genetic makeup of an organism in order to get a required phenotype(physical characteristic).
Genetic engineering technologies
There are several forms of technology which are used to edit the genome of an organism. One of the most common is Clustered Regularly Interspaced Short Palindromic Repeats(CRISPR) gene editing.
CRISPR technology was adapted from the natural defense mechanisms of bacteria. When there is a failed viral attack on bacterial cells, a portion of the virus genetic information is stored in the DNA of the bacteria. Bacteria are then able to use this nucleotide sequence as well as a protein known as Cas 9 to destroy the virus if the same type of virus infects the bacteria. This is done as it is able to recognise the identical genetic sequence of the stored DNA and cut out this portion of virus DNA rendering the virus useless as it will be unable to function properly.
The use of CRISPR in genome editing
Scientists have found that this system can be used to edit the genome of an organism. In order to do this scientists first identify a section of DNA that they want to edit, so for example it could be a nucleotide sequence with the nitrogenous bases ATC ATC ATC. They would then need to create a specific guide RNA that is complementary to this sequence, so in this case it would be TAG TAG TAG. The guide RNA is attached to the enzyme CAS 9 which is responsible for cutting the DNA that needs to be edited. It locates the target DNA which is complementary to the gRNA and cuts the DNA. Scientists are then able to modify the genome by inserting new sequences of DNA into the gap.
Development of CRISPR editing
While there have been many successes in gene editing using CRISPR, one of the main issues lies around the inheritance of the edited sequence/gene. ‘DNA that is transmitted from one parent, from one generation to the next via classic laws of heredity, is inherited by only half the progeny of each generation. This keeps the frequency of that genetic modification or trait in the population the same’ (Crisanti and Kyrou, 2018). Scientists at Imperial College London are developing an advanced form of CRISPR known as a gene drive. ‘Gene drives are inherited by more than 50% of the progeny. This gives them the ability to progressively increase the frequency of a trait over subsequent generations, which is an advantage over the use of other forms of genetic Genetic engineering’ (Crisanti and Kyrou, 2018).
Top: CRISPR/Cas9-based gene drives carry a molecular scissor, called Cas9 endonuclease, and a guide RNA (gRNA), which are essential for cutting the DNA at a specific site within the genome. Human and mosquitoes carry two copies of each gene for every trait. When the DNA is cut, the repair machinery copies information from Allele 1 - which carries the code for the gene drive and the cargo DNA that causes female sterility - to the broken Allele 2. In this way the gene drive is present in every mosquito in the progeny. Bottom: Following the classic laws of inheritance, traits (red) are inherited by only half the progeny from each generation (left), which is not enough to spread the trait within a population. In animals modified with a gene drive, the trait is spread to all the progeny in every generation. As the modified animals mate with other wild-type members of the species (blue), the trait quickly spreads to all the members of the population.
(Crisanti and Kyrou, 2018)
Exploring gene drives in a Practical Sense
Professor Andrea Crisanti and Kyros Kyrou of Imperial College London made an article about using gene drives to control wild mosquito populations and wipe out malaria. Only female mosquitoes bite humans as they need nutrients to produce their eggs. When an infected female bites, the Plasmodium parasite is passed into the bloodstream infecting the person bitten.The gene drives ‘targets fertility genes that are essential for the development of the female mosquito. When these genes are changed the female is unable to bite or produce offspring’ (Crisanti and Kyrou, 2018). Experiments have been successful as they were able to spread this trait to 100% of the mosquito population that they had in captivity.
My interest in this topic
After learning about the gene drives I had a few questions primarily focused around the possibilities that a gene drive created. I asked the writer of the article and was met with a reply by a pHD student of his. As gene drives can be used to edit the genome of an organism I was interested in whether it was possible to increase immunity against the parasite. I was met with the following reply "This is a great idea and something a number of our colleagues are working on. Unfortunately it may be more complicated to make an effective gene drive spreading immunity to the parasite than one designed to kill the mosquito vector. When the idea was conceived in 2003, both ideas were considered but we realised there were more advantages to a “suppression” gene drive than the immunity kind (at least at the moment). Some of the reasons include: 1) parasites are probably much more able to develop resistance to an immunity gene drive than mosquitoes are against a suppression gene drive, 2) If parasites do evolve to evade the immunity, might they become more virulent? 3) Mosquitoes carry a number of different parasites (i.e. different types of malaria, lymphatic filiariasis) so by killing the mosquito you tackle many different diseases at once, 4) gene drives designed to suppress a population will disappear over time whereas gene drives designed to modify the population with an immunity gene will stay in the population indefinitely".
Conclusion
Genetic modification is a topic that I find very interesting. The possibilities it opens up are endless and in the next few years we could see it help cure many diseases. If you’re interested in this topic I would advise watching these videos:
Furthermore, there are many online resources and articles that can help develop your knowledge on the topic. I would strongly advise looking into genetic engineering as it may very well be more widespread in the future. If you have any questions feel free to ask them in the Biology forum.
References
Crisanti, A. and Kyrou, K., 2018. Using Gene Drives To Control Wild Mosquito Populations And Wipe Out Malaria. [online] The Conversation. Available at: <https://theconversation.com/using-gene-drives-to-control-wild-mosquito-populations-and-wipe-out-malaria-104613> [Accessed 6 June 2020].
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