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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];