The New Dogma of Genetics?
  • Shihab Mohammad

The New Dogma of Genetics?

Gene-editing has always been projected, in the media at least, as a futuristic technology that could revive extinct species create unicorns or custom design babies. While that is definitely an exaggeration that doesn’t fit in with the current scope of research in this field, there are multiple applications of gene-editing that have the potential to revolutionize the field of medicine.


CRISPR (pronounced “crisper”) is short for Clustered Regularly Interspaced Short Palindromic Repeats. Don’t let that put you off, it may seem like a mouthful but isn’t really that difficult to understand. Palindrome stands for a word that is spelled the same both backward and forward (like “Hannah”). The genome of any organism consists of nucleotides A, G, C, and T. Hence in this context, a palindromic gene may appear as “CGAAGC”. When these palindromic sequences are repeated multiple times, let’s say in the genome of a bacteria. These repeats are separated by sequences called spacers, which serve an important role in storing genetic code from past invaders. The idea is explained in the illustration below, wherein a protospacer sequence from a bacteriophage (an invader) is incorporated into the bacterial genome for the future detection of this particular invader. We can intuitively think of them as memory cells that are acquired in a human body after vaccination to fight off pathogenic invasion (although their functioning is fundamentally different).



[1]


When the virus invades again, post identification, the bacteria sends Cas (CRISPR associated) proteins to destroy the virus. These Cas proteins are guided to their destination by an RNA sequence called gRNA or guide RNA. Since there are multiple proteins that belong to this Cas family, scientists were then tasked to find out the most efficient one amongst them and they decided to go ahead with Cas 9, the widely used term CRISPR-Cas9 comes from therein.


Researchers are harnessing this CRISPR-Cas9 complex from bacteria in order to edit human genomes. Consider the case of a genetic disease such as sickle cell anemia, in which there’s a particular gene that is causing the disease. This Cas9 complex can simply be sent to knockout the variant that is causing the disease and replace it with a healthier one. This technology essentially treats the human genome like a word processor, using which one may delete, cut, copy, or paste. Very often, the researchers have to design the gRNA sequences in silico (using computer software) and then use laboratory tools such as PCR amplification to manufacture and administer to test subjects (in most cases, mice). The results are then analyzed using statistical methods to test for their significance. Most Cas experiments involve the following, that are essential to their functioning:


  1. gRNA: that locates the problematic part of the gene that needs to be replaced

  2. Cas9 enzyme: that ensures isolation of this gene

  3. An engineered piece of DNA fragment that will replace the problematic part.


There are multiple types of CRISPR methods that may be employed to treat a variety of defects:

  • Knockouts: These are used to disrupt a gene permanently. As the genomic sequence is translated for protein function. Disabling a gene can stop the production of the protein that is not required.

  • Edit: This is the most commonly used one as it allows us to rectify mutation in the genes. This is particularly useful for treating patients that have been exposed to radioactive material and as a result, have had their DNA altered or damaged.

  • Repression: This is similar to knocking a gene out, except that we do not remove it permanently rather chemically modify it to inactivate it. Chemical modification of genes happens naturally in the human body, wherein methylation (addition of –CH3 group) can inactivate a gene. However, in this case, it is done artificially to inactivate parts of the genome that an organ may not require.

  • Activation: This is complementary to the idea of repression and involves chemical modifications such as phosphorylation (addition of a phosphoryl group) among many others.

In the current COVID pandemic, CRISPR based technologies are at the helm of developing new testing and diagnostic methods [2]. The enzyme used for COVID-19 detection is the Cas-12 protein. While still in its infancy, CRISPR offers us a wide variety of options to tackle autoimmune diseases and may even evolve one day to cure infections, previously assumed incurable. Due to an exponentially growing interest in gene –editing, the buzzword of modern medicine may come to practice faster than previously estimated.


Works Cited

LeMieux, Julianna, et al. “COVID-19 Drives CRISPR Diagnostics.” GEN, 1 May 2020, www.genengnews.com/insights/covid-19-drives-crispr-diagnostics/.


CB Insights. “What Is CRISPR?” CB Insights Research, CB Insights, 7 Feb. 2019, www.cbinsights.com/research/what-is-crispr/.

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