Genetic Engineering

• The term ‘Genetic Engineering’ was coined in 1951 by Jack Williamson. 
• It is the process of direct human manipulation of the organism’s genome.  
• It involves introducing the foreign DNA into the organism of interest to add one or more traits that aren’t found naturally in the organism. 
• The organism thus produced is known as GMO or Transgenic organism.

• Genome is relatively resistant to change. To deter any changes from being inadvertently made to DNA, cells have inherent mechanisms to proofread and repair their genetic code. Remarkably, researchers have taken advantage of the cell’s DNA repair mechanisms to achieve genome editing. 
• To accomplish this, scientists can use 
  • Artificially engineered enzymes called nucleases act as molecular scissors and are used to crack open DNA strands.  
  • Once the break is introduced in DNA, the cell will detect the problem & quickly activate repair machinery. 
  • DNA sequence designed to be inserted is also sent along with a nuclease, such that when a cut is made in the DNA, the cell’s own repair mechanism can use the DNA sequence supplied to replace an existing DNA sequence. 
• This method allows scientists to change the genetic makeup of cells directly.  

Genetic material can be inserted from the same species as well as other species. Accordingly, they are known as Transgenic and Cisgenic GMOs.

1. Gene delivery tools

• Genes are inserted into the body using vectors which are usually viruses.
• Viruses can produce other problems like
  • Toxicity
  • Immune response
  • Inflammatory response
  • Gene control and  targeting issues

2. High costs

• The whole process is quite expensive and hence not inclusive. It will create the division in society between haves and have-nots.

3. Ethical Dilemma

• Principal concerns include morality, eugenics helping the fittest to survive, ongoing clinical debates about informed consent, religious debate, the possible rise of clones, designer babies, and possibly super-humans.

4. Informed consent

• In the case of germline therapy, it is impossible to obtain informed consent as the patients affected by the editing are the embryo and future generations.

5. Limited knowledge of the functions of the genes

Scientists know functions of limited genes, and worst is in some cases, scientists don’t know whether a particular gene is performing more than one function

6. Others

• It might lead to designer babies & the commodification of children.
• It can be used in biological warfare.
• Recreation of extinct species can lead to disasters.
• If a wrong DNA segment is inserted and if it gets expressed, it can cause new diseases in human beings.

Side Topic: Gene Knock Out

A gene ‘knock out’ is a genetically engineered organism that carries one or more genes in its chromosomes that have been made inoperative.

Currently, four families of engineered nucleases (Molecular Scissor) are used: 

• Mega nucleases
• Zinc finger nucleases
• Transcription Activator like  Effector based Nucleases (TALENs)
• CRISPR- Cas System (Most advanced & important)

CRISPR/Cas9 System of Germline Editing

• CRISPR Cas 9 technology works like a cut-and-paste mechanism on DNA strands. The DNA strand identifies the specific location of the genetic codes that need to be changed or “edited” and then, using the Cas9 protein, which acts like a pair of scissors, that location is cut off from the strand. Once the DNA strand is broken, it has a natural tendency to repair itself. During the auto-repair process, Scientists intervene by supplying the desired sequence of genetic codes that binds with the broken DNA strand.
• Nobel Prize for Chemistry in 2020 was awarded for discovering the CRISPR Cas9 scissor.
• It is a revolutionary technique for Gene Editing with very high efficacy 
  • CRISPR: It is the mechanism that Bacteria uses to protect themselves from viruses. In this system, DNA is plucked out of Virus and inserted in little bits into the bacterium’s chromosome. In this way, Bacteria records the viruses it has been exposed to so that cells are protected from those viruses in the future. 
  • Cas 9 is a cutting enzyme. 

Stage 1

Guide RNA is shepherded with Cas 9 System 

• RNA is used to guide Cas 9 to the targeted position.
• Cas 9 is used to make a cut. 

Stage 2

• Cas 9 locks onto DNA & unzips it (both strands are divided).

Stage 3

• Cas 9 snips the DNA, creating a break in both strands.

Stage 4

• The DNA will repair itself using an inbuilt repaid mechanism using a piece of single-stranded DNA injected into the cell that binds itself with the broken DNA strand.

Why it is revolutionary

• It is cheaper (than already existing gene-editing technology).  
• It has very high efficacy.

Uses and Problems now

Its applications are immense, and it has made the designer baby a reality. Since it will have a wide range of ethical and social implications, inventors Jennifer Doudna and Emmanuelle Charpentier have called for Moratorium until proper consensus on its use is made. 

• Cure to diseases: CRISPR Cas-9 technology is used to treat many incurable diseases. It includes the cure for Sickle Cell Anaemia, diabetes, inherited eye diseases, and various types of cancers.
• Controlling number of mosquitos: Scientists have used the CRISPR technique to produce sterile male mosquitos of species that are responsible for spreading diseases such as malaria, dengue, zika etc. 
• Some scientists call for bringing extinct species back to life using this technology, like the Oxford Universities project on reviving Mammoth.
• Designer Babies: Bioethicists fear abuse of gene editing by the private sector, preying on a parent’s desire to create a perfect child. In 2018, a Chinese researcher disclosed that he had altered the genes of a human embryo to prevent the infection of HIV. It was the first documented case of creating a ‘designer baby’, and it caused widespread concern in the scientific community.
• Issue of Informed Consent: Bioethicists have also raised the concern that it is impossible to obtain up-to-date consent for germline therapy because the patients affected by the edits are the embryo and future generations.
• Inclusivity Issue: Only wealthy people will be able to afford this technology, increasing existing disparities and creating another class of haves and have-nots.