Gene Editing

Gene Editing

This article deals with ‘Gene Editing  – UPSC.’ This is part of our series on ‘Science and Technology’ which is important pillar of GS-3 syllabus . For more articles , you can click here

Definition

Genome editing is an approach in which the genome sequence is directly changed by adding, replacing, or removing DNA bases  .

Method

• 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 been able to take 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 break is introduced in DNA, cell will detect the problem  & quickly activate repair machinery.
  • DNA sequence designed to be inserted is also send 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 directly change genetic makeup of cells 

Uses in Humans

Gene Therapy	Somatic Cell Gene Therapy – Gene Therapy in normal cells Person will be treated for particular disease Germ Cell Gene Therapy – Gene Therapy in Germline Cells For next generation – Next generation will not be affected by genetic disorder
Enhancement genetic engineering	Insertion of a gene to try to ‘enhance’ a known characteristic; for example, the placing of an additional growth hormone gene into a normal child
Eugenic genetic engineering	attempt to alter or ‘improve’ complex human traits, each of which is coded by a large number of genes; for example, personality, intelligence, character, formation of body organs, and so on.

Note : Similarly, Gene Editing can be done in Plants and Animals to alter their genetic makeup and giving them desired characteristics and make Genetically Modified Crops and Animals

Concerns

Gene delivery tools	Genes are inserted into body using vectors which are usually viruses Viruses can produce other problems like – Toxicity – Immune response – Inflammatory response – Gene control and  targeting issues
High costs	Whole process is quite expensive and hence not inclusive
Playing with god
Informed consent	It is impossible to obtain informed consent for germline therapy because the patients affected by the edits are the embryo and future generations.
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 particular gene is performing more than one function
Might lead to designer babies & commodification of children

There are currently four families of engineered nucleases (Molecular Scissor) being 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 is the revolutionary technique for Gene Editing with very high efficacy
  • CRISPR : It is mechanism which Bacteria uses to protect itself from viruses . In this system, DNA is plucked out of Virus and inserted in little bits into chromosome of bacterium. In this way, Bacteria records over time the viruses it has been exposed to so that cells are protected from those viruses in future .
  • Cas 9 is cutting enzyme

Stage 1	Guide RNA is shepherded with Cas 9 System RNA to guide Cas 9 to Targetted position Cas 9 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 break in both strands
Stage 4	Cell repairs the break using piece of single stranded DNA injected into the cell

Why CRISPR technology is revolutionary

• It is cheaper (than already existing technology)  
• Efficacy is very high
• Made production of designer baby a reality
• Treatment of diseases which are caused by faulty gene sequences like CFTR 
• Livestock improvement
• Bioremediation

Uses and Problems now

• Its applications are immense and it has made designer baby a reality . Since it will have wide range of ethical and social implications, inventors Jennifer Doudna and Emmanuelle Charpentier have called for Moratorium on it till proper consensus on its use is made .
• Scientists are calling for bringing extinct species back to life using this technology like Oxford Universities project on reviving Mammoth .