Recording-2025-03-12T01:41:58.900Z Lecture 12.6

Overview of Gene Editing

• Gene editing is a powerful biotechnology tool that allows specific, precise changes to DNA.

• Can be used in laboratory and living organisms.

• Recent FDA approval for the first gene editing treatment, highlighting its growing role in medicine.

• Significant potential to change lives through medical applications.

CRISPR-Cas9 System

• CRISPR: Stands for Clustered Regularly Interspaced Short Palindromic Repeats.

  • A naturally occurring bacterial immune system used as a gene editing tool.

  • More adaptive than traditional restriction enzymes found in other biotechnologies.

• Functioning in Nature:

  • Bacteria infected by a virus capture a piece of the viral DNA and store it in their genomic CRISPR sequence.

  • On subsequent infections, the CRISPR RNA guides the Cas9 enzyme to cut the viral DNA, disabling it.

  • Allows bacteria to remember and respond to recurring viral threats.

  • This adaptive immunity is inherited by descendants of the bacterium, offering protection across generations.

• Applications of CRISPR-Cas9:

  • Modify specific DNA nucleotides to fix mutations causing genetic diseases.

  • Potentially transform treatment strategies for various genetic disorders, such as sickle cell disease.

Mechanism of Action in Gene Editing

• Editing Process:

  1. CRISPR sequence is designed to match a specific target gene.

  2. Cas9 enzyme is introduced along with guide RNA.

  3. Cas9 cuts the DNA at the specified site, creating a double-stranded break.

• Cellular Repair Mechanisms:

  • Cells aim to repair breaks using intact DNA as a template (if available).

  • If no template is provided, cells may attempt random repairs, often resulting in nonfunctional genes.

• Outcomes of Editing:

  • Gene Repair: Provide desired DNA sequence as a template for correct repair, restoring healthy gene function.

  • Gene Knockout: Without a repair template, random insertion may knock out gene function, potentially eliminating harmful effects.

Real-World Applications and Future Potential

• FDA Approval: The first CRISPR-based therapy (Caskevi) approved for treating sickle cell disease, marking a breakthrough in genetic treatments.

• Ongoing Research: Hundreds of clinical trials addressing various conditions:

  • Blood disorders (e.g., sickle cell, beta thalassemia).

  • Eye disorders, genetic blindness treatment.

  • Cancer therapies, especially for blood cancers.

  • Addressing bacterial and viral infections through gene knockout strategies.

  • Metabolic disorders, including cystic fibrosis.

Broader Implications in Science

• Photosynthesis Research: Attempting to improve photosynthesis efficiency for higher crop yields.

• Diagnostic Innovations: Development of easy-to-use CRISPR-based diagnostic tests, potentially transforming rapid testing for diseases like COVID-19 by combining the speed of rapid tests with the accuracy of PCR tests.

Conclusion

• Gene editing, particularly through CRISPR-Cas9, holds transformative potential for medicine and biological research.

• The technology represents one of the most significant advancements in biotechnology since antibiotics, with ongoing developments likely to further revolutionize healthcare.