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FnCas9

Challenges of CRISPR
• CRISPR, a natural bacterial defence mechanism, has been adapted for genome editing in higher organisms.
• It uses a guide-RNA (gRNA) to direct the Cas9 enzyme to a specific DNA sequence for cutting, triggering the cell’s repair system to insert the correct sequence.
• However, the CRISPR-Cas9 system, especially with the SpCas9 enzyme from Streptococcus pyogenes, can cause off-target effects, cutting unintended genome parts.

  • Scientists from the CSIR-Institute of Genomics and Integrative Biology, New Delhi, have developed an enhanced genome-editing system, FnCas9, which can modify DNA more precisely and efficiently than existing CRISPR-based technologies.
  • To address issues with CRISPR, researchers are exploring the FnCas9 enzyme from Francisella novicida, known for its precision but lower efficiency.
  • Researchers at CSIR-IGIB have modified and engineered new versions of FnCas9 to enhance its efficiency without compromising its specificity.
  • Experiments showed that the enhanced FnCas9 cut target DNA at a higher rate than the unmodified version.
  • It also performed better in identifying single-nucleotide changes in the genome, increasing the scope for detecting disease-causing genetic changes.
  • Testing against genetic disorders like Leber congenital amaurosis type 2 (LCA2), the enhanced FnCas9 successfully corrected mutations in retinal cells, showing high efficiency and minimal off-target effects.

Dig Deeper: Read about the basics of the Genome-editing system.

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