#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

• The human genome was sequenced 25 years ago, what’s the delay in editing? We know the sequence of the genes but we don’t know what most of the genes do, nor do we fully understand the coding and non-coding sequence (yet)
• CRISPR is an adaptive immune system: After the first infection, the bacteria has been ‘vaccinated’ against the virus
  • The next time the virus comes around, it will inject its genetic information into the bacteria but now the bacteria in the CRISPR area have a signature of the virus
• Difficulties in application of CRISPR: CRISPR uses a guide RNA to recognize the virus DNA but delivery of the Cas + guide RNA needs to be precise and the protein is too large to insert with ease
  • But, solving the delivery issue doesn’t mean CRISPR is suitable for all diseases; its most potent application is for genetic mutations (and likely not cancer which has many different mutations in the cell)
• Future goals of CRISPR technology: Creating more feasible Cas and guide RNA delivery system; inserting large genes into the genome, precisely and efficiently
• Ethical considerations of gene editing germline:
  • Slippery slope argument: If we allow X and Y, we will enter an unchartered territory with designer babies, making babies smarter (which we don’t know how to do), etc.
    • It’s worth noting that athletics, and intelligence, are more complicated than we want to believe; even with the right genetics, environment plays a huge role in realizing genes
  • Thinking about how the line should be drawn: Is there an obvious and important medical benefit?

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Feng Zhang, a professor of neuroscience at MIT and a pioneering figure in gene editing, joins Peter to discuss his groundbreaking work in CRISPR technology, as well as his early contributions to optogenetics. In this episode, they explore the origins of CRISPR and the revolutionary advancements that have transformed the field of gene editing. Feng delves into the practical applications of CRISPR for treating genetic diseases, the importance of delivery methods, and the current successes and challenges in targeting cells specific tissues such as those in the liver and eye. He also covers the ethical implications of gene editing, including the debate around germline modification, as well as reflections on Feng’s personal journey, the impact of mentorship, and the future potential of genetic medicine.

We discuss:

• Feng’s background, experience in developing optogenetics, and his shift toward improving gene-editing technologies [2:45];
• The discovery of CRISPR in bacterial DNA and the realization that these sequences could be harnessed for gene editing [10:45];
• How the CRISPR system fights off viral infections and the role of the Cas9 enzyme and PAM sequence [21:00];
• The limitations of earlier gene-editing technologies prior to CRISPR [28:15];
• How CRISPR revolutionized the field of gene editing, potential applications, and ongoing challenges [36:45];
• CRISPR’s potential in treating genetic diseases and the challenges of effective delivery [48:00];
• How CRISPR is used to treat sickle cell anemia [53:15];
• Gene editing with base editing, the role of AI in protein engineering, and challenges of delivery to the right cells [1:00:15];
• How CRISPR is advancing scientific research by fast-tracking the development of transgenic mice [1:06:45];
• Advantages of Cas13’s ability to direct CRISPR to cleave RNA and the advances and remaining challenges of delivery [1:11:00];
• CRISPR-Cas9: therapeutic applications in the liver and the eye [1:19:45];
• The ethical implications of gene editing, the debate around germline modification, regulation, and more [1:30:45];
• Genetic engineering to enhance human traits: challenges, trade-offs, and ethical concerns [1:40:45];
• Feng’s early life, the influence of the American education system, and the critical role teachers played in shaping his desire to explore gene-editing technology [1:46:00];
• Feng’s optimism about the trajectory of science [1:58:15]; and
• More.

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