BIOLOGY Science & Technology
In fewer than 5 years, CRISPR has revolutionised the face of biology. What is CRISPR? How it happens? How big of a deal is it? How does it change the future? All you needed to know about it.
The last few years has seen remarkable progress in genetic engineering as scientists around the world have developed a revolutionary approach in gene editing which involves precise cutting and pasting of DNA by specialised protein - CRISPR, that could allow us to cure diseases like the Sickle cell Anemia and Muscular Dystrophy. You might have heard of the term CRISPR, the short for Clustered Regularly Interspaced Short Palindromic Repeats, is generally used to refer CRISPR-Cas9.
How it happens?
While you're trying to CRISPR a genome, the CRISPR system guides a protein called Cas9 which is able seek out, cut and degrade the viral DNA, after which the cellular repair processes kick in and the repair processes are then convinced to make the desired edits. It's a three-step process. In the first step, CRISPR uses a guide molecule of RNA, which is a 105 letter long, 20 of which matches the target sequence in a gene to find the infected area. The second stage swaps out the guided RNA and directs Cas9 to the site. Finally, the cutting starts for either of two reasons - editing or deleting, after which a new, fresh gene will be obtained. While deleting, the bad genes are deactivated and in case of editing, template of a DNA is pasted.
Why is it revolutionary? How big a deal is it?
Let's consider the Huntington Disease. This disease is caused by an autosomal dominant mutation in either of an individual's two copies of a gene called Huntingtin. This means a child of an affected person typically has a 50/50 chance of carrying the faulty gene. The Huntingtin gene provides the genetic information for a protein that is also called "huntingtin". Here, CRISPR can be used to break up this Huntingtin gene and repair it and cure the person of this disease. The Huntington Disease has a frequency of 4-15 in 100,000 (european descent)[Info Source: Wikidata]. This process of gene editing can be used in a vast number of cases of other diseases as well, such as the Sickle Anemia. We have been putting DNA into organisms for a long time now. But what's impressive is that with this technology we have a modular targeting system which will help us put the DNA exactly where we want. CRISPR can be applied to any living organism including human embryos. So then we can change an entire species forever right?
Genetic Engineering is not new. It's been in the development since the 70s. CRISPR gives us the ability to enhance properties of a species like stronger bones, desired eye color. Currently, the knowledge of the genes that facilitate these properties are unknown but this does lead us to moral and ethical complexities. The inventors of CRISPR, Jennifer Doudna and Emmanuelle Charpentier called for a pause and discuss the ethics behind this technology in the scientific communities around the world while there have been arguments saying it'd be unethical to withhold this kind of a technology which can cure devastating genetic diseases.
Yes that's a valid argument. So why not do it?
The Chinese researchers while using CRISPR-Cas9 technology faced a huge setback while experimenting as they discovered off-target mutations in the genome which occured when the CRISPR-Cas9 targeted DNA sequences that are homologous to the target sequences. This made them abort the experiment at a premature stage. This kind of actions can prove to be disastrous. In 2015, the nuclease Cpf1 was discovered in the CRISPR/Cpf1 system of the bacteriumFrancisella novicida. Cpf1 showed various differences from Cas9 one of which is making a 'staggered' cut in double stranded DNA as opposed to the 'blunt' cut by Cas9, relying on a 'T rich' PAM (providing alternate targeting sites to Cas9) and requiring only a CRISPR RNA (crRNA) for successful targeting. On the other hand, Cas9 requires both crRNA and a transactivating crRNA (tracrRNA).
CRISPR opens its doors to non-therapeutic modifications leading to loss of diversity and eugenics. CRISPR was used to disrupt a gene which changed the black coat colour of the mice suggesting the possibility of inducing a pigmentation change in humans through embryonic editing. So, this genetic modification of a specific appearance could cause considerable physical and mental health to the children since their appearance is imposed on them through means other than blood relationship (designer babies).
The scientific communities should engage in a discussion to set guidelines of research and activities involving genetic modification of human germ cells which should make a clear distinction between genome editing in germ cells and in somatic cells.
By the end of 2017, over 5000 published research papers mentioned CRISPR. Some scientists in Philadelphia showed that they could use the technology to remove the DNA of an integrated HIV virus from infected human cells. A particularly active area of CRISPR research and experiments is the genetic manipulation of patient-derived stem cells to create models for diseases like Parkinson's, cystic fibrosis, cardiomyopathy and ischemic heart disease. It also allows researchers to correct disease-causing mutations in patient-derived pluripotent stem cells to create isogenic cell lines to differentiate to any cell type of interest for disease research, and has also helped to figure out important anomalies in gene-disease relationships. This technology has also been used to study Candida Albicans, to modify yeasts used to make biofuels and to genetically modify crop strains.
Current scientific achievements show that CRISPR isn't only a versatile technology, its bettering as time moves forward. A lot of progress needs to be made as there are technical and ethical challenges prevailing. With its current capabilities, we may see a future where we feed upon genetically engineered food, eliminated genetic disorders or may even bring extinct animal species back to life.
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