Why in the news?

Scientists have successfully used CRISPR-Cas9 gene editing to restore vision in individuals with a rare form of inherited or congenital blindness.

The groundbreaking clinical trial, named “BRILLIANCE,” demonstrated promising results in improving vision and quality of life for participants with Leber congenital amaurosis (LCA), a severe vision disorder.

What is Leber Congenital Amaurosis (LCA)?

LCA is a rare genetic disorder that primarily affects the retina the ‘light-sensitive’ tissue at the back of the eye. It leads to severe visual impairment or blindness at birth or within the first few months of life.
It is inherited in an autosomal recessive manner, meaning a child needs to inherit one defective gene from each parent to develop the condition.
There are several genes associated with LCA, with mutations in at least 14 different genes known to cause the disorder.
These genes generally affect the development and function of photoreceptors or the retinal pigment.

The BRILLIANCE trial involved 12 adults and two children diagnosed with LCA, a condition characterized by early-onset vision loss.
Participants received a single dose of a CRISPR gene therapy called EDIT-101, designed to correct mutations in the CEP290 gene responsible for LCA.
In this case, CRISPR-Cas9 cuts out the faulty DNA segment in the CEP290 gene and replaces it with a healthy DNA sequence, restoring the function of the CEP290 protein crucial for vision.
Out of 14 participants, 11 experienced improved vision without serious side effects.

CRISPR-Cas9 stands for Clustered Regularly Interspaced Short Palindromic Repeats and CRISPR-associated protein 9.
It is a technology that allows geneticists and researchers to edit parts of the genome by altering sections of the DNA sequence.
Emmanuelle Charpentier and Jennifer Doudna’s work on CRISPR-Cas9 as a ‘molecular scissor’ earned them the 2020 Nobel Prize in chemistry.
The system consists of two key components:

Cas9: This is the enzyme that acts like a pair of molecular scissors. It is responsible for cutting the DNA strand at a specific location, allowing for the removal, addition, or alteration of DNA at that site.
Guide RNA (gRNA): This is a piece of RNA that is designed to find and bind to a specific sequence of DNA that matches its code. The gRNA guides the Cas9 enzyme to the exact spot in the genome where an edit is desired.

Mechanism:
- The process begins with the design of a gRNA that matches the DNA sequence where an edit is needed.
- Once inside the cell, the Cas9 enzyme and the gRNA form a complex that can identify and bind to the target DNA sequence.
- The Cas9 then cuts the DNA at this location.
- After the DNA is cut, the cell’s natural repair mechanisms can be harnessed to add or remove genetic material, or to make specific changes to the DNA.

[2019] What is Cas9 Protein that is often mentioned in news?

(a) A molecular scissors used in targeted gene editing

(b) A biosensor used in the accurate detection of pathogens in patients

(d) A herbicidal substance synthesized in genetically modified crops