cover of episode #323 - CRISPR and the future of gene editing: scientific advances, genetic therapies, disease treatment potential, and ethical considerations | Feng Zhang, Ph.D.

#323 - CRISPR and the future of gene editing: scientific advances, genetic therapies, disease treatment potential, and ethical considerations | Feng Zhang, Ph.D.

2024/10/28
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Feng Zhang: 本期节目探讨了CRISPR基因编辑技术的起源、发展和应用，以及相关的伦理问题。Zhang博士详细介绍了CRISPR系统的运作机制，包括Cas9和Cas13蛋白的功能，以及PAM序列在避免自身靶向中的作用。他还讨论了CRISPR技术在治疗镰状细胞贫血等遗传疾病中的应用，以及递送系统在基因治疗中的重要性。此外，他还探讨了基因编辑技术的伦理问题，包括生殖系编辑的争议。最后，Zhang博士分享了他个人的科研经历，以及对科学未来发展的乐观展望。 Peter Attia: Attia博士与Zhang博士就CRISPR基因编辑技术进行了深入探讨，涵盖了该技术的科学原理、应用前景和伦理挑战。Attia博士对光遗传学技术和CRISPR技术进行了比较，并探讨了基因编辑技术在治疗遗传疾病方面的潜力和局限性。他还关注了基因编辑技术的伦理问题，特别是生殖系编辑的风险和社会影响。此外，Attia博士还探讨了科学发展与社会责任之间的关系，以及如何平衡科学进步与伦理规范。

Deep Dive

Key Insights

Why did Feng Zhang shift his focus from optogenetics to gene editing?

He realized the biggest bottleneck in optogenetics was precise gene insertion into specific brain cells, which required easier gene editing technology.

How did CRISPR revolutionize gene editing?

CRISPR made gene editing more feasible and democratized by allowing easy design of strategies to edit DNA, unlike cumbersome zinc finger and TALEN technologies.

What are the current challenges in delivering CRISPR-based therapies?

The main challenge is efficient delivery of CRISPR components to the right cells and tissues, especially for large proteins like Cas9.

How does Cas13 differ from Cas9 in its function?

Cas13 targets and cleaves RNA viruses, unlike Cas9 which targets DNA viruses, and has a suicide feature that cleaves all RNA in the cell upon activation.

What ethical concerns are associated with germline gene editing?

Concerns include the potential for unintended mosaicism, lack of long-term safety data, and the slippery slope towards designer babies and non-medical genetic modifications.

How did Feng Zhang's early education influence his career path?

His exposure to molecular biology in a Saturday enrichment class and a volunteer program at a gene therapy lab sparked his interest in science and gene editing.

What role does Feng Zhang see for AI in future scientific advancements?

AI can accelerate science by analyzing large datasets, predicting protein structures, and automating experimentation, leading to more rapid and efficient discoveries.

Chapters
Feng Zhang discusses his early work in optogenetics and the challenges he faced in gene editing, leading him to focus on improving gene-editing technologies.
  • Feng Zhang developed optogenetics with Karl Deisseroth at Stanford.
  • The biggest bottleneck in optogenetics was precise targeting of different brain cells.
  • This led Zhang to focus on making gene editing more accessible and precise.

Shownotes Transcript

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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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