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October 28, 2024 • 2hr 5min
#323 - CRISPR and the future of gene editing: scientific advances, genetic therapies, disease treatment potential, and ethical considerations | Feng Zhang, Ph.D.
The Peter Attia Drive
Feng Zhang, professor of neuroscience at MIT and pioneering figure in gene editing, discusses his groundbreaking work in CRISPR technology. The conversation covers the origins of CRISPR, its revolutionary impact on gene editing, current therapeutic applications, technical challenges, and ethical considerations around genetic modification.
#323 - CRISPR and the future of gene editing: scientific advances, genetic therapies, disease treatment potential, and ethical considerations | Feng Zhang, Ph.D.
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Key Takeaways
- CRISPR is a bacterial immune system that has been adapted into a powerful gene editing tool
- The technology works by using guide RNA to direct Cas proteins to make precise cuts in DNA sequences
- Major challenges remain around delivery methods for getting CRISPR components into specific cells/tissues
- Current clinical applications focus on liver diseases, eye diseases, and blood disorders like sickle cell anemia
- Ethical concerns exist around germline editing that would affect future generations
- The field needs better delivery systems and more validation before widespread therapeutic use
Introduction
Feng Zhang, professor of neuroscience at MIT and pioneering figure in gene editing, discusses his groundbreaking work in CRISPR technology. The conversation covers the origins of CRISPR, its revolutionary impact on gene editing, current therapeutic applications, technical challenges, and ethical considerations around genetic modification.
Topics Discussed
Origins of CRISPR and Early Work (10:45)
CRISPR was first discovered in bacterial DNA sequences in the 1980s as repeating patterns. Key developments included:
- Initial discovery of clustered regularly interspaced palindromic repeats in bacterial genomes
- Recognition that spacer sequences matched viral DNA, suggesting immune function
- Identification of CRISPR-associated (Cas) proteins that could cut DNA
How CRISPR Works as an Immune System (21:00)
The bacterial CRISPR system provides adaptive immunity against viruses through several mechanisms:
- First viral infection: Bacteria capture viral DNA segments and incorporate them between CRISPR repeats
- Subsequent infections: Bacteria use guide RNA matching stored viral sequences to direct Cas proteins to cut viral DNA
- PAM sequence requirement prevents bacteria from cutting their own DNA
Development as a Gene Editing Tool (36:45)
Zhang describes how CRISPR was adapted for gene editing:
- Previous tools like zinc fingers and TALENs were difficult to engineer
- CRISPR advantage: Easy to program with different guide RNAs
- Analogy to smartphones: CRISPR is like hardware that can run different software (guide RNAs)
Current Therapeutic Applications (48:00)
Several diseases are being targeted with CRISPR therapy:
- Blood disorders: Sickle cell disease treatment through bone marrow modification
- Liver diseases: Using lipid nanoparticles for delivery
- Eye diseases: Direct injection for conditions like LCA2 and LCA10
Technical Challenges and Future Directions (1:00:15)
Major obstacles remain in developing CRISPR therapies:
- Delivery methods: Getting components into specific tissues
- Protein size: Current Cas proteins are too large for some delivery vehicles
- Efficiency: Need better rates of successful editing
- Cost: Manufacturing and scaling challenges drive high treatment costs
Ethical Considerations (1:30:45)
Discussion of ethical implications including:
- Germline editing concerns about modifying future generations
- Medical necessity vs enhancement applications
- International regulation and oversight of gene editing
- Societal implications of genetic modification
Personal Journey and Education (1:46:00)
Zhang shares his background and influences:
- Early education in Iowa after moving from China
- Importance of teachers and mentors in fostering scientific interest
- Value of hands-on learning and research opportunities
- American education system enabling pursuit of scientific interests
Conclusion
CRISPR technology represents a revolutionary advance in gene editing with enormous therapeutic potential. While technical challenges around delivery and efficiency remain, ongoing research and development continue to expand its capabilities. Careful consideration of ethical implications will be crucial as the technology advances toward wider clinical application.