TIGR: The Gene-Editing Tool That Could Outdo CRISPR
Summary of the video “The Successor to CRISPR May Be Even More World Changing” by SciShow.
Feng Zhang, the scientist who pioneered CRISPR gene editing in humans, is now studying TIGR-Tas, a system found in viruses and bacteria that may surpass CRISPR by reading both strands of DNA, achieving single-letter precision, and being small enough to reach harder-to-treat tissues like the brain.
From Curiosity to CRISPR Pioneer
Zhang's Path: Computer Tinkerer to Molecular Biologist
Feng Zhang's parents were computer scientists who encouraged him to take things apart and figure out how they work. In seventh grade, he discovered molecular biology and realized DNA works like computer code—logical principles govern both. This mindset led him from building PCs as a pre-teen to studying green fluorescent protein in high school, then using it to track virus infection in college.
CRISPR: The Bacterial Immune System Turned Gene Editor
CRISPR (clustered regularly interspaced short palindromic repeats) is a natural immune defense in bacteria and archaea. It works like a molecular cut-and-paste tool: a guide RNA finds matching DNA sequences, brings along a cutting enzyme (Cas protein), and removes the target DNA. Zhang adapted this bacterial system to edit genes in larger organisms, including humans.
CRISPR's Clinical Breakthrough
By 2025, CRISPR had been investigated for at least 18 disorders including sickle cell and leukemia. The most dramatic milestone came when it was used for the first time to rewrite DNA in a living infant's liver cells, providing a life-saving treatment. Typically, scientists edit cells in the lab and return them to patients, but this case rewrote DNA directly in the body.
Why CRISPR Isn't Perfect
CRISPR's Limitations: Single Mutations and Precision
CRISPR works well for single-gene disorders but struggles with complex diseases caused by multiple genetic factors, like Alzheimer's or Parkinson's. Additionally, CRISPR opens a 5 to 8 letter-long window of DNA, preventing single-letter precision edits. Delivery to hard-to-reach tissues like the brain also remains challenging since CRISPR requires cells to be dividing, and brain cells divide slowly.
The Liver Advantage: Why Early CRISPR Success Was Location-Dependent
The 2025 infant treatment targeted liver cells because the liver is easy to reach—the body naturally sends foreign particles there for detoxification. Liver cells also divide frequently, which CRISPR needs to function. Diseases affecting slower-dividing tissues like the brain remain much harder to treat with current CRISPR approaches.
Enter TIGR-Tas: The Next Generation
What Is TIGR-Tas and Where It Comes From
TIGR (tandem interspaced guide RNA) is a system Zhang's team discovered in viruses and some bacteria. Like CRISPR, it contains short repeating DNA sequences plus a protein that cuts DNA, but the repeats are not exact—gaps between them hold guide sequences that direct the system to targets. Scientists still don't fully understand TIGR's natural function, but it may be part of bacterial-viral warfare, with viruses using it to insert into bacterial genomes and bacteria using it to defend.
TIGR-Tas's Four Key Advantages Over CRISPR
TIGR-Tas reads both strands of the DNA double helix when targeting, making it more accurate. It is physically smaller than Cas9, allowing better delivery to distant tissues. It can create smaller windows of DNA accessibility, enabling single-letter precision edits that CRISPR cannot achieve. Its compact size makes it easier to package into viral vectors for brain and nervous system delivery.
TIGR-Tas's Potential for Brain Diseases
Because TIGR-Tas is more compact and doesn't require rapidly dividing cells, it could treat neurological disorders like ALS, Huntington's disease, and Parkinson's—diseases where problematic cells are hard to reach or divide slowly. Zhang's team is actively studying how to best deliver TIGR-Tas into the brain to unlock treatment for these previously intractable conditions.
How Scientists Study TIGR-Tas
The Experimental Pipeline: From Synthesis to Human Cells
Zhang's team synthesizes the entire TIGR-Tas DNA sequence and transplants it into E. coli bacteria to grow it in the lab. They then either purify the TIGR-Tas protein for controlled test-tube studies or insert the system directly into human cells grown in petri dishes to observe what happens. This allows them to measure the system's behavior in increasingly complex environments.
Centrifuges and Viral Vectors: Lab Tools for Delivery
To deliver gene-editing systems into organisms like mice, researchers use hollowed-out viruses called viral vectors. These tiny particles must be concentrated using centrifuges that spin at up to 100,000 times Earth's gravity—a force so extreme that a human subjected to it would be crushed. This extreme spinning separates and concentrates the viral particles needed for delivery.
Zhang's Philosophy and Vision
Basic Research as the Foundation for Breakthroughs
Zhang practices basic science—studying how biological systems work at a fundamental level without an immediate application in mind. He starts with hypotheses about what bacteria or viruses can do, then systematically explores their capabilities. Only after understanding the system does he engineer it into a tool. This approach has repeatedly led to world-changing discoveries, from CRISPR to TIGR-Tas.
Nature as the Ultimate Engineer
Zhang believes nature has already solved countless biological problems over millions of years of evolution. His strategy is to study these natural solutions, understand how they work, and then engineer them into useful biotechnology. This approach has proven far more effective than trying to invent solutions from scratch.
Notable quotes
You can actually see with your eyes how something is changing, or how a cell or an animal is behaving. — Feng Zhang
When we find the answer we're the first person in the world to know the answer to something. And that is satisfying because you are kind of pushing the frontier. — Feng Zhang
Nature is very wise, you know, it has all these really cool innovations and solutions to all of these different problems. — Feng Zhang