Why is it in the News?

Scientists utilized a CRISPR-Cas9 tool to restore vision in individuals, including adults and children, afflicted with congenital blindness termed Leber congenital amaurosis (LCA).

What is Leber Congenital Amaurosis?

• Leber Congenital Amaurosis (LCA) is a rare genetic eye disorder where affected infants experience severe vision loss or blindness at birth.
• The condition results from the impaired function of light-gathering cells (rods and cones) in the retina.

Prevalence and Cause:

• LCA affects approximately one in 40,000 people.
• It is caused by a gene mutation that disrupts the proper function of the CEP290 protein, which is critical for vision.

Recent Development:

• Scientists have employed CRISPR-Cas9 gene editing technology to develop a novel therapy called EDIT-101.
• In a clinical trial called "BRILLIANCE," participants received a single dose of EDIT-101.
• The treatment involves cutting out the mutation in the CEP290 gene and replacing it with healthy DNA, restoring the normal function of the CEP290 protein and allowing the retina to detect light.
• This groundbreaking approach offers a promising treatment for individuals affected by LCA.

What is CRISPR-Cas9?

• CRISPR-Cas9 is a unique technology that enables geneticists and medical researchers to edit parts of the genome by removing, adding or altering sections of the DNA sequence.
• It is currently the simplest, most versatile and precise method of genetic manipulation.

How does CRISPR-Cas9 work?

• The CRISPR-Cas9 system operates through two primary molecules:
  • Cas9, an enzyme often likened to "molecular scissors," which can precisely cut both strands of DNA at a designated location in the genome.
  • Guide RNA (gRNA), a segment of RNA containing a specific pre-designed sequence (about 20 bases long) within a longer RNA scaffold.
  • The scaffold binds to DNA, while the pre-designed sequence guides Cas9 to the intended genomic location, ensuring accurate DNA cleavage.
• The guide RNA is tailored to identify and bind to a particular sequence in the DNA, with RNA bases that complement those of the target DNA sequence.
  • This specificity ensures that the guide RNA binds solely to the target sequence and avoids other genomic regions.
• Once bound, Cas9 cuts across both DNA strands at the targeted location.
  • Subsequently, the cell's repair mechanisms recognize the DNA damage and attempt to rectify it.
• Scientists exploit this DNA repair process to introduce alterations to one or more genes within the genome of a selected cell.