Genome editing has moved from experimental concept to FDA approved medicine in less than a generation. Few people have been closer to that transformation than TJ Cradick.

TJ was one of the earliest pioneers in programmable biology, helping shape the field from the era of zinc finger nucleases through the rise of CRISPR and next generation editing systems. As the second employee and Head of Genome Editing at CRISPR Therapeutics, he helped lay the scientific foundation for Casgevy, the first FDA approved CRISPR therapy. Later, at Excision BioTherapeutics, he worked on some of the first in vivo CRISPR therapies targeting latent HIV reservoirs.

In this episode, we dive deep into the evolution of genome engineering. We explore the transition from protein engineered nucleases to scalable CRISPR guide libraries, and the growing importance of delivery technologies capable of targeting tissues beyond the liver. TJ explains how off target analysis evolved from primitive assays into massively parallel sequencing pipelines and why the future of gene editing depends just as much on delivery and manufacturing as the editing enzymes themselves.

We also discuss the hidden challenges behind FDA approval, the realities of scaling genome editing therapies, the future of in vivo editing, and the ethical questions surrounding human germline engineering.

This conversation is a rare look inside the engineering, regulation, and philosophy of one of the most transformative technologies humanity has ever developed.

· 0:00 - Science Fiction to Science Fact

· 0:23 - Cutting Edge of Science

· 0:37 - Introduction to TJ Cradick

· 1:06 - CRISPR Therapeutics and Beyond

· 1:42 - Early Interest in Science

· 2:12 - Academic Journey

· 3:08 - Transition to Biotech

· 4:04 - Zinc Finger Nucleases

· 5:28 - Evolution of Screening Technologies

· 6:48 - CRISPR Libraries and High Throughput Screens

· 8:07 - New Technologies in Gene Editing

· 9:15 - Off-Target Effects and Assays

· 11:23 - Future Opportunities in Gene Editing

· 13:18 - Regulatory Challenges

· 16:24 - Cost Challenges in Genome Editing

· 18:22 - Manufacturing and Delivery Innovations

· 20:14 - Delivery Challenges and Innovations

· 22:30 - Capsid Design and Blood-Brain Barrier

· 24:01 - Viral vs. Non-Viral Delivery Systems

· 27:19 - IP Limitations and CRISPR Variants

· 30:31 - Target Selection for Therapeutics

· 34:03 - Precise Repair Technologies

· 37:03 - Off-Target Effects in Gene Editing

· 42:31 - Genetic Instability in Edited Cells

· 46:20 - Human Germline Engineering

· 49:19 - CRISPR for Viral Cure

· 51:27 - Regulatory Path Improvements

· 54:20 - Balancing Speed and Safety

· 57:03 - Advice for Future Scientists