Natural Vs Unnatural – CRISPR Technology, The Genetic Scissors
CRISPR technology can also help combat AIDS through a separation from the hiding place of the DNA of the HIV virus – the inactive or latent type – that prevents the removal of the virus by most of the existing treatments.
For discovering and improving the CRISPR-Cas9 genome editing, Emmanuelle Charpentier and Jennifer Doudna won the Nobel Prize in Chemistry in 2020. Genome editing is a form of genetic engineering where DNA in the genome of a living organism is added, suppressed, changed, or substituted at sites. Geneticists have long been using chemicals or radiation to induce mutations, but these have not been regulated. This was followed by gene targeting, which is very costly and takes a long time to generate a mutation.
Currently, four main groups of engineered gene editing endonucleases exist: zinc finger nuclease (ZFN), transcription activator-like effector nucleases (TALENs), and engineered microbial origin meganucleases; and the endonuclease CRISPR-Cas9. CRISPR-Cas9 is the easiest, most powerful, and reliable genetic modification tool that is the source of a bustle in the field of science.
It was developed by the analysis of some bacteria with a similarly integrated system to respond to invasive viruses, similar to an immune system. CRISPR uses bacteria to snatch and hold pieces of the DNA virus back in order to help them detect and protect against the virus when it strikes next time.
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This mechanism contains two main molecules: a Cas9 enzyme, which is the ‘molecular scissors’ for the purpose of cutting the two strands of DNA in a particular position, and one RNA (gRNA) guide, which is around 20 bases long and directs the Cas9 to the right part of the genome to be cut.
This latest technology provides countless opportunities that go beyond human health alone. CRISPR technology in agriculture has been most frequently used to decrease food waste by simply “publishing” characteristics (not genetically modifying) such as prevention of mushroom browning when cuts are made. CRISPR can help plants in hostile conditions to survive.
For example, the cacao plantations in West Africa are often threatened – by unhealthy weather; and by the cruel reality of being predated by the mealybug insect that spreads the ‘cacao swollen virus disease’ infection. CRISPR will help cacao become immune to contamination and save it from extinction – so that in the years to come, we do not have to risk our chocolate consumption! In addition to producing more fruit, advocates of CRISPR are seeking to create additional foods that are more desirable to the customer than junk foods – such as baby carrots or seedless watermelons through a package of potato chips.
Gene editing for the processing of coffee beans naturally decaffeinated in order to maintain the taste and nutrition have a much more beneficial effect than the vigorous earlier drinking and steaming. A group of researchers in the Netherlands changed the DNA of wheat to extract gluten and make it suitable for celiacs.
CRISPR makes advances in preventing food allergies by rewriting the regions of a gene recognized by the immune system to induce an allergic reaction and safely consume milk, eggs, or peanuts. A new variety of more robust and yielding spicy tomatoes has emerged to produce spicy salsa by integrating capsaicin genes from chili peppers into tomatoes! The opportunities are endless.
CRISPR gene editing may increase the development of algae biofuels. Algae strains have been developed which produce twice as much fat and are subsequently used to produce biodiesel by removing genes that restrict fat production. This biodiesel production becomes more economically feasible because the algae turn CO2 into biofuel more efficiently.
Pet owners continue to use the technology to fix genetic diseases that abound in pure race dogs. Dalmatians, for example, have a genetic defect that makes them vulnerable to bladder stones. Other breeding programs are underway for pet pigs and koi carps in custom sizes, colors, and designs. Faster, stronger, and better jumping breed horses are predicted to be produced by altering the myostatin gene, which is a protein crucial to muscle development.
This could have an influence, not only on Polo but also on the records of the Olympics. A research group in Norway used CRISPR to produce sterile salmon which enhances their growth and is more disease resistant. The quality of Omega-3 in these fish can be increased to provide healthier and nutritious choices. CRISPR may also assist in monitoring the number of animal species that transmit infectious diseases or those that are invasive in a specific environment by developing ‘genetic drives’ to ensure that gene alteration is inherited from offspring that propagate over many generations throughout the animal population.
Researchers have shown this technology to be effective in controlling mosquitoes that transmit malaria and hope similar attempts are soon to be made against invasive rats and feral cats. The technology is being used on the other end of the continuum to bring back extinct species – de-extinction. Beginning with the development of hybrids that resurrect passenger pigeons, a Harvard project group aims to bring the wooly mammoth that went out thousands of years ago back to life!
Theory suggests that CRISPR technology may help us handle any genetic mutation at will, curing the disease it causes. But we are only at the beginning of this technology growth as a treatment and there are so many unknowns. Technologies in cancer research have accelerated studies to target gene-induced cancer, develop animal models, recognize drug-resistant genes, and deliver targeted molecular medicinal products.
Technology shows promise in the treatment of blood disorders such as sickle cell disease and beta-thalassemia by extracting patient bone marrow stem cells and transforming fetal hemoglobin production to increase blood oxygen and avoid repeat blood transfusions. Hemophilia research is also in advanced stages. A particular mutation triggers many inherited blindnesses, making it easy to instruct CRISPR-Cas9 to target a single gene and change it.
The most common cause of hereditary childhood blindness, Leber congenital amaurosis is researched for the purpose of correcting the most recurrent associated mutation and restoring the function of light-sensitive cells until a child fully loses view. Cystic fibrosis, a severe disorder of respiratory origin that decreases the patient’s lifetime significantly through supportive treatment, has been found to be related to and potentially corrected by mutations located in a gene named CFTR.
The DMD gene for muscular dystrophy of Duchenne and the neurodegenerative condition, Huntington’s gene-component disease have been extensively researched to incorporate gene-editing therapies ranging from shorter protein gene to gene self-destruct. Scientist uses the technology very cohesively to build a multi-event analog CRISPR recording system or tape recorder for DNA; and a molecular instrument called CAMERA for monitoring a cell’s lifetime and exposure to antibiotics, nutrients, viruses, and light that could help to understand a variety of complex processes in a living organism.
CRISPR technology can also help combat AIDS through a separation from the hiding place of the DNA of the HIV virus – the inactive or latent type – that prevents the removal of the virus by most of the existing treatments. Another strategy is the use of a mutation in the CCR5 gene that encodes for a protein at the immune cell surface that is used by the HIV virus to infect the cells by a person resistant to HIV infections.
In a somewhat controversial case in China, this technique has recently been used to edit human embryos and confer genetic resistance to HIV from HIV-positive fathers, to HIV-negative mothers to in vitro fertilization that led to the birthright of the ‘CRISPR boys,’ Lulu and Nana. The scientist, He Jiankui, has created legal and ethical controversies behind this groundbreaking work of cell editing (which could be passed down from generation to generation) instead of limiting himself to experimenting with somatic (non-reproductive) cells, leading to his conviction coupled with imprisonment and heavy fines.
UC Berkeley and Gladstone Institutes scientists have created a new CRISPR-based diagnostic test Covid-19 that can deliver a positive or a negative result with a smartphone camera in just 15 minutes. It also provides the viral load, a number of viral particles in a sample, and an estimation of how infectious the patient might be in recovery or quarantine times. In India, in cooperation with the CSIR-IGIB (Institute of Genomics and Integrative Biology), Tata used this technology to develop the test by the name of FELUDA, with high-quality standards with a 96% susceptibility and 98% specificities for the detection of the novel coronavirus. Unlike conventional vaccines and therapies, the therapeutic role of the CRISPR Cas13 in SARS-CoV-2 infection has been considered by the identification and degradation of the intracellular viral genome by the PAC-MAN approach, but it has still not been highlighted.
Despite being much more accurate than its predecessors, CRISPR also created unintended DNA modifications or off-target edits and could lead to mosaicism or not even editing of all cells. Before widespread clinical use, particularly in the editing of embryos, these problems still have to be overcome. Monitoring the consequences of these ‘edits’ has ethical issues for decades to come – because children who have not yet been born cannot receive approval – a problem without a solution!
The international commission on guidelines; the exchange and validation of knowledge and a clearly defined whistleblowing channel, which ideally will make the next effort for human germline editing a scientific success – not an unethical embarrassment. As co-inventor Jennifer Doudna puts it herself, “the ability to influence the genetic future of our species is amazing and awful. It could be the greatest challenge we have ever faced to determine how to handle this. We will have to find ways to incorporate CRISPR safely in 2021 and beyond.”