Gene Editing: Everything You Need To Know

Panaimaram

DNA (deoxyribonucleic acid) is the carrier of genetic information and is present in living organisms as the main constituent of chromosomes. It basically defines the distinctive characteristics of someone or something. This characteristic is technically identified to be unchangeable . Gene editing is a new development in the field of medical science that involves the rewriting and alteration of DNA . The study has faced quite a number of controversial situations wherein people have been assuming that 'designer babies' are what would be the in thing in the next decade. Read on to know more about the truth behind gene editing and how it is being used to rewrite the code of life.

Also known as genome editing, gene editing involves insertion, deletion or replacement of DNAs at specific sites in the genome of an organism. It is mostly done using engineered nucleases (molecular scissors) . With gene editing, scientists can correct harmful mutations, disable target genes and alter the activity of specific genes .

Genes are responsible for making and maintaining the proteins and enzymes that form the base of building tissues and organs. Genes are strands of genetic code, which is denoted by letters G, C, T and A. There's a nucleus in every cell in the human body and there are about 20,000 genes that are bundled into 23 pairs of chromosomes. These chromosomes are all coiled up in the nucleus. It is only about 1.5 percent of our genome (genetic code) that is made of genes. 10 percent of the genetic code regulates the genes and how it turns on in the right cell or at the right time.

The letters of the genetic code refer to the molecules and can be deciphered as:

Inside the DNA, the molecules are paired up:

These are the base pairs of the DNA double helix. Every human inherits 60 new mutations from the parents, most of them coming from the father.

Gene editing gained a lot of attention when its potential to prevent and treat human diseases was announced by researchers. It is known that there are several genetic disorders that tend to pass on from one generation to the next. These genetic disorders are most of the time quite serious, weakening and life-threatening as well. Going by statistics, one in every 25 children is born with a genetic disorder/disease. The most commonly occurring genetic diseases are muscular dystrophy, cystic fibrosis and sickle cell anaemia .

The corrupt DNA of the patient's cells are rewritten through gene editing in order to treat the disorder . However, the concern stays with the fact that it can do much more than just repairing the faulty genes.

Gene editing has already proven to be a success in case of modifying people's immune cells in order to fight cancer. It has also shown great results in modifying cells such that there is a development of resistance towards HIV infection . Researchers are acting quick on finding ways to fix defective genes in human embryos so that babies born do not possess inherited serious illnesses. However, this research has opened the gates for quite a lot of controversy, especially because the genetic changes affect the sperm or the egg cells and in such cases of genetic edits, a bad or incorrect move could result in a side effect being passed on to future generations .

The agricultural industry has achieved utmost benefit from the concept of gene editing. Incorporating features of gene editing in agricultural procedures have made things cheaper, faster and more precise. Gene editing has made several research studies take shape. It has allowed the making of seedless tomatoes, gluten-free wheat and mushrooms that do not turn brown even when old, etc .

Pharmaceutical companies have also taken the benefit of gene editing. Companies that deal with next-generation antibiotics have created harmless viruses that are designed to attack particular strains of infection-causing bacteria .

Gene editing has been applied to pig organs so that they can be made safe to be transplanted into humans .

Gene editing has enabled scientists to understand the operating mechanism of almost all kinds of genes .

Although there are different ways of editing genes, the one that showed the maximum potential and made a breakthrough is a molecular tool known as Crispr-Cas9 (Crispr: Clustered Regularly Interspaced Short Palindromic Repeats, Cas: CRISPR-associated). This tool uses 'the Crispr bit' (a guide-like molecule) which enables the finding of a specific part in an organism's genetic code (for instance, a mutated gene). This part is then cut off by Cas9 (an enzyme). In case the cell tries to repair the damage then it usually ends up making a hash of it, eventually disabling the gene.

However, to mend faulty genes, scientists remove the mutated DNA and replace it with a healthy strand. This is injected simultaneously along with the Crispr-Cas9 molecules. Researchers have also studied the effectiveness of other enzymes that are close in functionality to that of Cas9 - such as Cpf1 (this enzyme can edit DNA quite effectively).

To understand the working methodology of how Crispr facilitates gene editing, consider the below steps:

1. A person with a genetic disorder receives an injection (in the bloodstream or affected tissues) containing millions of particles.

2. The particles injected could either be harmless or nanoparticles carrying the gene editing molecules.

3. Each of the injected particle contains
a guide molecule (the one that finds the DNA to be changed),
an enzyme to cut the target DNA, and
healthy DNA to repair the mutated gene.

4. The particles first enter the affected cells and eventually the nuclei where the DNA is present.

5. Once the particle has entered the cell nucleus, the guide molecule looks around for a match. The guide molecule sticks to this targeted region and makes the edit possible.

6. After the target is found, the enzyme begins to play its role and cuts the DNA into half. This is where the cell identifies the damage and tries to repair itself.

7. The breakage is repaired by inserting the healthy DNA in its place.

As the gene editing molecules are quite big, they do find it difficult to get into the cells. The ideal way of making this possible is by packing the gene editing molecules into viruses that are harmless but are designed to infect particular kinds of cell. Millions of these are injected directly into the person's affected tissue or in some cases into the bloodstream. The virus invades the target cells and releases the gene editing molecules which then starts doing its work .

Although there has been limited research on mankind in this field, some of the successful ones are:

use of fatty nanoparticles to carry Crispr-Cas9 molecules to the liver .
use of tiny zaps of electricity to open up pores in embryos enabling the entry of gene editing molecules .

Contrary to some of the believes stating that gene editing needs to be done only within the human body, some scientists have come up with research results showing how it can be performed outside the body. In some of the gene editing trials, researchers collected cells from the patients' blood, followed by making the necessary genetic edits . The modified cells were then infused back into the patients. This technique looks promising in treating people with HIV (because for patients with HIV, the virus infects and kills all the immune cells once it enters the body - this happens when HIV latches on to the proteins present on the surface of the immune cells). Immune cells can be collected from the patients' blood and gene editing performed to cut out the DNA that the cells would ideally need to make the surface proteins. If the protein is absent, the HIV virus would not be able to enter the cells .

A similar approach has been tried in fighting specific types of cancer. The immune cells present in the patients' blood are collected and edited such that they can produce surface proteins capable of binding and killing the cancer cells. Researchers grow masses of such cancer-killers in the laboratory and infuse them in the body of the patient .

When done outside the body, there are less chances of going wrong. A thorough check can be conducted to check the editing process before they are put back into the patient's body.

No, although quite precise, modern gene editing is not perfect. There have been several cases of trial and errors that showed big hits and misses. It is highly possible that when gene editing, some cells are easily reached while some are not. Even if the guide molecule takes the right route and the desired cells are found, there is a high possibility that edits could differ from one cell to the other. There could be errors such as ending up mending two copies of mutated gene in one cell while only one copy in another cell. Such issues create problems when a single mutated gene is the cause behind the genetic disorder. Other problems could happen when edits get made at an incorrect region in the genome. Such off-target edits can turn dangerous, especially when they disrupt healthy genes or the regulatory DNA.

Several studies have given the opinion that it would not be long before gene editing goes much beyond mending faulty genes in children and adults. It is believed that gene editing could address issues of dangerous mutations in embryos. Few scientists tried covering this in the form of an experimental study and supported gene editing in human embryos to treat and prevent the occurrence of serious diseases .

However, there is no scope for mistakes when preparing to try gene editing with embryos because the edits done would pass on to the future generations as well. This concept has given rise to the feeling of having engineered babies in the near future. Also, speculations exist where many believe that there would come a time where designer babies would be created to address social aspects rather than medical, such as the need to make a person more taller or more intelligent . However, designer babies is a thing of the future that is quite a distant dream now, especially considering the rounds of clinical trials and approvals that it would have to go through to be out in the open.

Irrespective of the controversies and the pros or cons of gene editing, it is worth mentioning that the efforts of the researchers would surely not be wasted. Gene editing is slowly gaining popularity and will be used in the modern day medical treatment soon to address almost all forms of genetic disorders . With the ample benefits of gene editing, mankind will surely benefit if it is used in the right way and in the right direction.

பனைமரம் - Panaimaram