India’s First Gene-Edited Sheep

India’s First Gene-Edited Sheep

Why in News? 

Recently, SKUAST-Kashmir has successfully produced India’s first gene-edited sheep. This step is a new achievement in the field of animal biotechnology. 

India’s First Gene-Edited Sheep: Key Points

• Sher-e-Kashmir University of Agricultural Sciences and Technology (SKUAST-Kashmir) has created history in the field of animal biotechnology by producing the country’s first gene-edited sheep.
• This unique research used the CRISPR-Cas9 technology, which is considered one of the most advanced and precise gene-editing systems today.
• The myostatin gene, which controls muscle growth in sheep, was selected in this process.
  • Through modification in this gene, the muscle mass of the sheep was increased by nearly 30%, a trait not naturally found in Indian sheep.
• All international biosafety protocols have been followed in this project.
• This sheep does not contain any foreign genes, which makes it different from transgenic organisms.

What is Gene-Editing Technology?

• Gene editing is a precise biotechnological process that allows desired changes in the DNA or RNA of any organism.
• This technology gives scientists the ability to alter the genetic code of an organism — whether by adding, removing, or modifying genes.
• Through this process, the genetic material is changed in a way that improves traits or functionality of the organism.
• The technology identifies the specific part of the gene that needs improvement and makes changes exactly at that location.
• Programmable nucleases play the main role in gene editing, which recognize the targeted DNA segment and create a double-strand break (DSB).
• Gene editing began in the 1990s, but its efficiency was limited at that time.
• There are three major types of engineered nucleases included in this technology:
  • Zinc Finger Nucleases (ZFN)
  • Transcription Activator-Like Effector Nucleases (TALENs)
  • Engineered Meganucleases
• Currently, gene editing is used in medicine for treating cancer, AIDS, and genetic disorders, and in agriculture to improve crop traits and disease resistance.

Major Genome Editing Techniques and Their Features

• Meganucleases: The biggest advantage of meganucleases is their small size, which makes them easy to deliver into the body using various viral vectors. The target DNA length is about 14 to 40 base pairs (bp). There may be some off-target effects with meganucleases.
• Zinc Finger Nucleases (ZFN): In ZFN technology, a pair of nucleases target a region about 18 to 36 bp long. It can be delivered through viral vectors, but G-rich regions pose a challenge for targeting. From a design perspective, it is more complex than meganucleases.
• Transcription Activator-Like Effector Nucleases (TALENs): TALEN technology targets about 28 to 40 bp DNA per pair. Each target DNA sequence must begin with 5ˈT for TALEN to work effectively.
• CRISPR-Cas9 System: CRISPR-Cas9 is the most popular and powerful technique today. It targets a DNA region of about 19 to 22 bp, which is shorter and more precise than other methods. In CRISPR, the target site is recognized based on a required sequence called PAM (Protospacer Adjacent Motif).

How Does CRISPR Technology Work?

• Natural Basis
  • CRISPR technology is originally based on the natural defense system of bacteria and single-celled microorganisms.
  • When these microbes are infected by viruses, they use the CRISPR system to protect their own DNA.
  • The key scientists behind this revolution, Jennifer Doudna and Emmanuelle Charpentier, were awarded the Nobel Prize in Chemistry in 2020.
• Cas9 Protein
  • A vital part of CRISPR technology is a protein called Cas9, often referred to as “molecular scissors.”
  • Doudna and Charpentier developed this technique so that the guide RNA (gRNA), which directs Cas9, can target any chosen DNA sequence.
• How is DNA Cut?
  • The Cas9 protein and guide RNA work together to precisely identify the target DNA.
  • As soon as Cas9 reaches the desired DNA segment, it cuts the double strand of the DNA.
  • This cut acts like biological scissors to create a clear break in the DNA pattern.
• Cell’s Response
  • There are two options:
    • Self-repair – The cell tries to rejoin the broken DNA using its repair mechanism.
      • During this process, errors often occur, which can disrupt the function of the gene or completely deactivate it.
    • Insert new DNA material – Scientists can supply a new DNA template, which the cell may integrate into its genome during the repair. 

Advantages and Disadvantages of Gene Therapy

• Advantages

• • • New treatment options: Gene therapy helps treat diseases where other drugs do not work. It offers a permanent solution for many disorders.
    • One-time treatment: Gene therapy is usually given only once, removing the need for repeated medication. It is more convenient than other treatments.
    • Long-lasting effects: The therapy can remove symptoms for a long time, improving the quality of life.
    • Benefit for generations: If faulty genes are removed through gene therapy, they will not pass from parents to children, reducing the chance of inherited diseases.

• Disadvantages

• • Expensive process: Gene therapy is very costly, making it inaccessible to many.
    • For example, Zolgensma, a drug for Spinal Muscular Atrophy, costs $2.1 million, making it one of the most expensive drugs in the U.S.
  • Potential dangers: If gene therapy reaches other cells in the body, it can be harmful.
    • Changes in reproductive cells can happen unintentionally, affecting future generations.

Risk of infection: Some gene therapies use inactive viruses to deliver healthy genes to faulty cells. This may carry a risk of viral infection.